Attorney Docket No. REGT-003/01WO 344478-2007 CAS-PHI COMPOSITIONS AND METHODS OF USE CROSS-REFERENCE TO RELATED APPLICATIONS [01] This application claims the benefit of and priority to U.S. Provisional Patent Application No.63/374,184, filed August 31, 2022, the contents of which are incorporated by reference herein in their entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING [02] The contents of the electronic sequence listing (REGT- 003_01WO_SeqListing_ST26.xml; Size 925,918 bytes; and Date of Creation: August 31, 2023) are herein incorporated by reference in their entireties. FIELD [03] The present invention generally relates to systems, methods and compositions used for the control of gene expression involving sequence targeting, that may use vector systems related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and components thereof. The present invention also generally relates to use of AAV vectors for the delivery of large payloads, such as CRISPR proteins (e.g., Cas-phi), guide RNAs, CRISPR-Cas or CRISPR systems. Additionally, the present invention relates to methods for developing or designing CRISPR-Cas systems-based therapies or therapeutics. BACKGROUND OF THE INVENTION [04] Engineered DNA-binding proteins that can be customized to target any gene in mammalian cells have enabled rapid advances in biomedical research and are a promising platform for gene therapies. The RNA-guided CRISPR/Cas9 system has emerged as a promising platform for programmable targeted gene regulation. Fusion of catalytically inactive, "dead" Cas9 (dCas9) to an effector domain generates a synthetic activator or repressor capable with highly specific and potent activation or silencing of target genes. [05] Adeno-associated virus (AAV) vectors have been proposed for gene delivery of CRISPR/Cas9 components for in vivo studies and therapeutic applications. AAV vectors provide stable gene expression with low risk of mutagenic integration events. AAV vectors can be engineered to target tissues of interest in vivo and are currently used in human clinical trials. However, gene delivery of S. pyogenes dCas9 in vivo is challenging because the size of the S. pyogenes dCas9 and an effector domain exceeds the packaging limits of standard AAV vectors. Accordingly, there exists a long felt and unmet medical need for alternative CRISPR systems, compositions and methods for use in in vivo studies and therapeutic applications. [06] Provided herein are compositions and methods comprising CRISPR and a catalytically deficient Cas-phi protein, which is smaller in size than a S. pyogenes dCas9 protein, thus addressing the unmet need. SUMMARY OF THE INVENTION [07] The present disclosure provides a composition comprising: a) a Cas-phi polypeptide or a polynucleotide sequence encoding the Cas-phi polypeptide, wherein the Cas-phi polypeptide comprises at least one RuvC domain and wherein the at least one RuvC domain is nuclease inactive and the RuvC domain comprises at least one mutation relative to a wildtype RuvC domain; and b) a polynucleotide sequence encoding a guide RNA (gRNA) that can specifically hybridize to a target nucleic sequence and to the Cas phi polypeptide to form a complex. In some embodiments the composition comprises: a) a Cas-phi polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4 and SEQ ID NO: 6, or a polynucleotide sequence encoding the Cas-phi polypeptide, wherein the Cas-phi polypeptide comprises at least one RuvC domain and wherein the at least one RuvC domain is nuclease inactive and the RuvC domain comprises at least one mutation relative to a wildtype RuvC domain; and b) a polynucleotide sequence encoding a guide RNA (gRNA) that can specifically hybridize to a target nucleic sequence and to the Cas phi polypeptide to form a complex. [08] In some embodiments, the Cas-phi polypeptide is a Cas-phi-1, a Cas-phi-2 or a Cas- phi-3 polypeptide. [09] In some embodiments, the at least one mutation is i) D394R, D394A or D394N; ii) E606R, E606A or E606Q; iii) D695R, D695A or D695N; iv) D394A and E606A; v) D394A and D695A; vi) D394A, E606A and D695A; or vii) D394R, E606R and D695R, numbered in accordance to SEQ ID NO: 4. In some embodiments, the Cas-phi polypeptide is a Cas-phi-2, and wherein the at least one mutation is i) D394A; ii) D394A and E606A; iii) D394A and D695A; or iv) D394A, E606A and D695A, numbered in accordance to SEQ ID NO: 4. [010] In some embodiments, the at least one mutation is i) D413A or D413N; ii) E618A or E618Q; iii) D708A or D708N; iv) D413A and E618A; v) D413A and D708A; or vi) D413A, E618A and D708A, numbered in accordance to SEQ ID NO: 6. In some embodiments, the Cas-phi polypeptide is a Cas-phi-3, and wherein the at least one mutation is i) D413A; ii) D413A and E618A; iii) D413A and D708A; or iv) D413A, E618A and D708A, numbered in accordance to SEQ ID NO: 6. [011] In some embodiments, the Cas-phi polypeptide is a Cas-phi-1, and wherein the at least one mutation is D371A, numbered in accordance to SEQ ID NO: 2. [012] In some embodiments, the Cas-phi polypeptide further comprises a deletion of a RuvC domain in comparison to a wildtype Cas-phi polypeptide, wherein the deletion of the RuvC domain is a RuvC-II domain deletion and/or a RuvC-III domain deletion. In some embodiments, the Cas-phi polypeptide further comprises a deletion of a zinc ribbon domain in comparison to a wildtype Cas-phi polypeptide. [013] In some embodiments, the Cas-phi polypeptide comprises the amino acid sequence of SEQ ID NO: 28, 30, 32, 34, 36, 38, 40, 42, 44, 160, 162, 164, 166, 168, 170, 172, 174, 176, 282, 284, 286, 288 or 290. In some embodiments, the Cas-phi polypeptide comprises an amino acid sequence at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or about 99% identical to the amino acid sequence of SEQ ID NO: 28, 30, 32, 34, 36, 38, 40, 42, 44, 160, 162, 164, 166, 168, 170, 172, 174, 176, 282, 284, 286, 288 or 290. [014] In some embodiments, the Cas-phi polypeptide or the polynucleotide sequence encoding the Cas-phi polypeptide is fused directly or indirectly to at least one effector domain or a polynucleotide sequence encoding the effector domain. In some embodiments, the Cas-phi polypeptide is fused indirectly to the at least one effector domain though a nuclear localization sequence and/or a linker sequence. [015] In some embodiments, the at least one effector domain is fused to i) the N-terminus of the Cas-phi polypeptide, ii) the C-terminus of the Cas-phi polypeptide, or iii) both the N- terminus and the C-terminus of the Cas-phi polypeptide. In some embodiments, the at least one effector domain fused to the N-terminus of the Cas-phi polypeptide and the C-terminus of the Cas-phi polypeptide are different. In some embodiments, the at least one effector domain fused to the N-terminus of the Cas-phi polypeptide and the C-terminus of the Cas-phi polypeptide are the same. [016] In some embodiments, the at least one effector domain comprises an effector domain derived from a mini VPR, p65 NF-Κβ transactivating subunit (p65), VP160, SET7, RTA, histone acetyltransferase p300, VPR, MyoDl, TET1 hydroxylase catalytic domain, LSDI, Cmi, AD2, CR3, GATA4, p53, MEF2C, TAX, PPARy, SET9, KRAB, DNMT3A, DNMT1, KRAB-MeCP2, SIN3A, Mxi1, SID4x or Dnmt3a3L or a combination thereof. [017] In some embodiments, the target nucleic acid sequence of b) is a regulatory region of a gene. In some embodiments, the regulatory region is a promoter or an enhancer. In some embodiments, the target nucleic sequence of b) encodes a gene product, and wherein the gene product is A4GALT, AAGAB, ABCD1, ACSL4, ACTC1, ACVRL1, ADNP, AFF2, AHDC1, AKT3, ALX4, ANK2, ANKRD11, ANOS1, AP1S2, APC, AR, ARCN1, ARHGEF9, ARID1A, ARID1B, ARID2, ARSE, ARX, ASH1L, ASXL1, ASXL3, ATP7A, ATP8A2, ATRX, AUTS2, AVPR2, AXIN2, BAG3, BCL11A, BCLAF1, BCOR, BMP4, BMPR1A, BMPR2, BRAF, BRCA1, BRCA2, BRIP1, BRWD3, BTK, CACNA1A, CACNA1C, CAMK2A, CAMK2B, CAMTA1, CASK, CASZ1, CCNQ, CDC42BPB, CDH1, CDKL5, CDKN1C, CFC1, CHAMP1, CHD2, CHD7, CHD8, CHM, CHRDL1, CHRM3, CIC, CLCN4, CLCN5, CNKSR2, CNTN4, CNTN6, CNTNAP2, COL11A1, COL1A1, COL2A1, COL3A1, COL4A5, COL5A1, CREBBP, CRYBB2, CSMD1, CTCF, CTNNB1, CTNND2, CUL3, CUL4B, CYBB, DCHS1, DCX, DDX3X, DICER1, DIP2A, DKC1, DLG2, DLG3, DMD, DMRT1, DNMT3A, DPP6, DSC2, DSCAM, DSG2, DSP, DYRK1A, EBP, EDA, EDNRB, EFNB1, EFTUD2, EHMT1, ELAVL2, ELN, EMX2, ENG, EP300, ERF, ERMARD, EXT1, EXT2, EYA1, EYA4, F8, F9, FANCB, FAS, FBN1, FGD1, FGF10, FGFR1, FLCN, FLG, FLNA, FMR1, FOXC1, FOXC2, FOXF1, FOXG1, FOXL2, FOXP1, FOXP2, FRMD7, FTSJ1, FZD4, GABRA1, GABRG2, GATA2, GATA3, GATA4, GATA6, GATAD2B, GCH1, GDF5, GDI1, GIGYF2, GJA5, GJA8, GK, GLA, GLI2, GLI3, GLMN, GNAS, GNB1, GPC3, GPHN, GRIA3, GRIN2A, GRIN2B, HCCS, HDAC4, HDAC8, HIST1H1E, HIVEP2, HIVEP3, HMGA2, HNF1B, HNRNPK, HNRNPU, HOXD13, HPRT1, IDS, IGF1R, IKBKG, IL1RAPL1, IQSEC2, IRF6, ITSN1, JAG1, KANSL1, KAT6A, KAT6B, KATNAL2, KCNH2, KCNQ1, KCNQ2, KDM5B, KDM5C, KDM6A, KDM6B, KIF11, KMT2A, KMT2B, KMT2C, KMT2D, L1CAM, LAMP2, LDLR, LEMD3, LHX4, LMNA, LMTK3, LMX1B, LRP5, MAGEL2, MAGT1, MAOA, MAP2K2, MBD5, MECP2, MED13L, MEF2C, MEIS2, MEN1, MID1, MITF, MLH1, MNX1, MSH2, MSH6, MSX2, MTAP, MTM1, MYBPC3, MYCN, MYH10, MYLK, MYT1L, NAA15, NBEA, NCKAP1, NDP, NEDD9, NEXMIF, NF1, NF2, NFIA, NHS, NIPBL, NKX2-5, NODAL, NR0B1, NR3C2, NR5A1, NRXN1, NSD1, NSDHL, NXF5, NYX, OCRL, OFD1, OPHN1, OTC, OTX2, PAFAH1B1, PAK2, PAK3, PAX2, PAX3, PAX6, PAX8, PAX9, PCDH19, PDHA1, PGK1, PHEX, PHF2, PHF21A, PHF3, PHF6, PHF8, PHIP, PIGA, PITX2, PKD1, PKD2, PKP2, PLP1, PMP22, PMS2, POGZ, POLR1D, PORCN, PQBP1, PRPS1, PTCH1, PTCHD1, PTEN, PTHLH, PTPN11, PURA, RAB39B, RAI1, RALGAPB, RASA1, RB1, RB1CC1, RET, RIMS1, RNF135, RP2, RPH3A, RPL15, RPS17, RPS19, RPS24, RPS26, RPS6KA3, RS1, RUNX1, SALL1, SALL4, SATB2, SCN1A, SCN2A, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SEMA3A, SETBP1, SETD1A, SETD2, SETD5, SF3B4, SGCE, SH2B1, SH2D1A, SHANK1, SHANK2, SHANK3, SHH, SHOX, SIM1, SIX3, SLC16A12, SLC16A2, SLC17A8, SLC2A1, SLC35A2, SLC4A10, SLC6A1, SLC6A8, SLC9A6, SMAD3, SMAD4, SMARCA4, SMARCB1, SMC1A, SMS, SNURF, SON, SOX10, SOX11, SOX2, SOX5, SOX9, SPAST, SPEN, SPINK1, SPRED1, SRCAP, SRY, STK11, STS, STXBP1, SYN1, SYNGAP1, SYP, TAB2, TAF13, TBL1XR1, TBR1, TBX1, TBX2, TBX20, TBX22, TBX3, TBX4, TBX5, TCF12, TCF20, TCF4, TCF7L2, TCOF1, TDGF1, TERT, TFAP2B, TGFBR1, TGFBR2, TGIF1, TIMM8A, TMLHE, TNNI3, TNRC6B, TP53, TP63, TRAPPC2, TRIO, TRIP12, TRPS1, TRRAP, TSC1, TSC2, TSPAN7, TWIST1, UBE2A, UBE3A, UBN2, UPF3B, USP9X, VEGFA, VHL, WAC, WDFY3, WDR45, WT1, XIAP, YAP1, YTHDC1, ZBTB18, ZC4H2, ZDHHC9, ZEB2, ZFPM2, ZIC1, ZIC2, ZIC3, ZIC4, ZMYND11, ZNF41, ZNF462, ZNF674, ZNF711 or ZWILCH. [018] In some embodiments, the target nucleic sequence of b) encodes a gene product, and wherein the gene product is MT-TL1, KCNQ2, DEAF1, SSBP1, KCNQ1, HNF1B, KAT6B, CDK8, MN1, COL4A1, CDKL5, VAPB, NALCN, TTR, RAC2, GJB2, MYO3A, MEIS2, BRCA2, NARS1, AIRE, GABRG3, RAD51, GATA6, PDX1, ETV6, BCL11B, CHEK2, WARS1, KAT6B, KCNQ1, PRNP, MAT1A, HCN4, DSG2, MAFB, ZSWIM6, WT1, NIPBL, COL9A3, MYH7, SMAD4, IL6ST, CAPN3, KCNK18, DDX3X, SCAMP5, APC, CEBPA, RBM20, PMS2, BEST1, HCN1, PKD1, MSH2, RAD50, EYA1, KCNQ2, PRKCE, SYT1, GNAS, GSDME, LMX1B, MECP2, LZTR1, KLHL7, SLC6A1, SUFU, CREBBP, KCNQ3, PPP2R1A, TOR1A, TGFBR1, COL5A1, SNAP25, GABBR2, SHANK3, PEX6, PPP2R5D, ATP1A3, KDM6A, TPM2, HNF4A, POLG, TUBB4A, PYGM, CPT2, BRCA1, LDLR, KCND2, NFKBIA, RPE65, PRPH2, BARD1, SDHD, PHKG2, MYL2, KCNK9, SPTB, TGFBR2, SSBP1, ATL1, CSF1R, SLC25A4, KAT6A, SATB2, POU3F3, SHOX, ENG, NOVA2, OTX2, PACS1, FBXO38, ALDH18A1, KCNC1, AARS1, CDKN2A, BBS7, PAX2, GNAO1, COL12A1, BLM, POGZ, TRPV4, FLG, FGFR1, KIF2A, ERF, EBF3, BRAF, RET, PDHA1, SPTAN1, PALB2, FASLG, TBC1D24, NOTCH3, FBN1, COL2A1, RRM2B, GLRA1, BMPR1A, MLH1, TCF3, THRB, CACNA1A, PKD2, ACVRL1, KIF5A, GLI3, KCNH1, GRIN2D, SHOC2, TP53, NTRK2, SPTLC1, GUCY2D, TPM1, CDH1, SPAST, NSD1, WFS1, PDE4D, PBX1, CBL, PMP22, DIAPH1, DMPK, GCK, KCNH2, TPP1, FANCC, FAS, BBS2, ABCC8, F11, KCNC3, MFN2, MPZ, CLCN1, PPP2CA, KCNJ2, SDHB, SPTBN2, CAPZA2, KLF1, NFIX, IFNGR1, COL1A2, MAPK8IP3, SCN5A, SRCAP, TP63, KCNA2, CDK13, CASQ2, TNNT1, DNM1L, SALL1, RHOA, KIF1A, RYR1, STAT3, HNF1A, COL7A1, PIK3CA, MYBPC3, CTCF, PTPN11, ATM, DEAF1, KCNT2, HMBS, ITPR1, TM4SF20, ASXL2, COL4A4, ADAR, DES, SCN2A, SLC4A1, HNF1B, BRIP1, FOXP1, KCNA1, MCCC1, BMPR2, MSH6, KRT9, MUTYH, RAF1, FH, ATAD3A, CASR, LMNA, REEP1, VHL, GATA2, DHDDS, ARID1A, NF1, RAD51C, KCNQ4, TNNT2, CXCR4, RYR2, ALPL, TPM3, SMN1, SERPINF1, PCGF2, SURF1, ATAD1, PTEN, TNFRSF11A, JAG1, ATP7B, CACNA1C, SLC16A2, SALL4, GJB6, MORC2, STING1, CHRNA4, TECPR2, GNA11, HEXB, HOGA1, DONSON, RRAS2, SLC6A8, SH3BP2, GNAQ, FLNA, PPP1CB, BICD2, ARID1B, PRKG1, TYR, ANKRD26, PHOX2B, EPAS1, PIK3R1, AFF4, MTOR, SAMD9L, ALK, SAMD9, PAH, PIEZO1, SOS2, STING1, HGSNAT, ABL1, AKT1, PDGFRB, GAMT, SLC35A3, CAMK2G, ATAD1, SURF1, IGHMBP2, GARS1, GLUD1, FGFR2, SMN1, FGFR3, MEFV, IDH2, KCNT1, VWF, GRIK2, SLC12A3, MAP2K1, KIF21A, PTEN, COG4, STAT1, CARD11, PMP2, SERPINF1, SPOP, STIM1, LAMB3, NLRC4, ITGB3, PNPO, CLCN2, SCN11A, NLRP3, IDH1, RIT1, TRIO, ADCY5, DNM2, SCN1B, SLC26A2, SCN8A, ALG1, KCNJ11, CHRNA1, MAP2K2, IFIH1, ACAD9, PKP2, CACNA1C, ORC1, UBTF, C3, KRAS, FANCA, FGF12, TIA1, HOXD13, CHRNB2, PSEN2, ACADM, MPL, SCN1A, GLMN, NRAS, RARB, PRKAR1A, SOS1, PCGF2, CACNA1E, PIK3CD or F5. [019] This disclosure provides a composition comprising: a) a modified Cas-phi polypeptide comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 28, 30, 32, 34, 36, 38, 40, 42, 44, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288 or 290, or a polynucleotide sequence encoding the modified Cas-phi polypeptide, and b) a polynucleotide sequence encoding a guide RNA (gRNA) that can specifically hybridize to a target nucleic sequence and to the Cas phi polypeptide to form a complex. [020] This disclosure also provides a vector comprising: the nucleic acid sequence encoding the Cas-phi polypeptide of (a) and the polynucleotide sequence encoding the gRNA of (b). In some embodiments, the gRNA is operatively linked to a promoter recognized by RNA polymerase III. In some embodiments, the gRNA is operatively linked to a human U6 promoter. [021] In some embodiments, the vector is a viral vector. In some embodiments, the viral vector is an adeno-associated virus (AAV) vector. In some embodiments, the vector is suitable for delivery via a non-viral delivery system. In some embodiments, the non-viral delivery system is a lipid nanoparticle or an exosome. [022] This disclosure also provides a viral particle comprising the vector of the disclosure. In some embodiments, the viral particle is a recombinant AAV (rAAV) particle. In some embodiments, the rAAV particle is an AAV9, AAV-PHP.eB, AAV-DJ, AAV2, MyoAAV, AAV1, AAV5, AAV6 or AAV8. [023] This disclosure also provides a population of viral particles comprising a plurality of viral particles of the disclosure. [024] This disclosure also provides a pharmaceutical composition comprising any one of the vector, the viral particle or the population of viral particles of the disclosure, and a pharmaceutically acceptable carrier, vehicle or diluent. [025] This disclosure also provides a cell comprising any one of the vector or the viral particle of the disclosure. In some embodiments, the cell is a mammalian cell or an insect cell. [026] This disclosure also provides a method of modifying the expression of a target gene in a population of cells comprising: contacting a population of cells comprising a target nucleic sequence encoding the target gene with any one of the vector, the viral particle, the population or the pharmaceutical composition of the disclosure, thereby modifying the expression of the target gene. [027] In some embodiments, the expression of the target gene is increased in the plurality of the modified population of cells in comparison to a population of cells contacted with any one of the vector, the viral particle, the population or the pharmaceutical composition of the disclosure; and a gRNA that does not specifically hybridize to the target nucleic acid sequence, but binds to the Cas-phi polypeptide to form a complex. In some embodiments, the expression of the target gene is increased by at least about 1.10-fold, at least about 1.15-fold, at least about 1.20-fold, at least about 1.25-fold, at least about 1.30-fold, at least about 1.35- fold, at least about 1.40-fold, at least about 1.45-fold, at least about 1.50-fold, at least about 1.55-fold, at least about 1.60-fold, at least about 1.65-fold, at least about 1.70-fold, at least about 1.75-fold, at least about 1.80-fold, at least about 1.85-fold, at least about 1.90-fold, at least about 1.95-fold or at least about 2.0-fold. [028] In some embodiments, the target gene is A4GALT, AAGAB, ABCD1, ACSL4, ACTC1, ACVRL1, ADNP, AFF2, AHDC1, AKT3, ALX4, ANK2, ANKRD11, ANOS1, AP1S2, APC, AR, ARCN1, ARHGEF9, ARID1A, ARID1B, ARID2, ARSE, ARX, ASH1L, ASXL1, ASXL3, ATP7A, ATP8A2, ATRX, AUTS2, AVPR2, AXIN2, BAG3, BCL11A, BCLAF1, BCOR, BMP4, BMPR1A, BMPR2, BRAF, BRCA1, BRCA2, BRIP1, BRWD3, BTK, CACNA1A, CACNA1C, CAMK2A, CAMK2B, CAMTA1, CASK, CASZ1, CCNQ, CDC42BPB, CDH1, CDKL5, CDKN1C, CFC1, CHAMP1, CHD2, CHD7, CHD8, CHM, CHRDL1, CHRM3, CIC, CLCN4, CLCN5, CNKSR2, CNTN4, CNTN6, CNTNAP2, COL11A1, COL1A1, COL2A1, COL3A1, COL4A5, COL5A1, CREBBP, CRYBB2, CSMD1, CTCF, CTNNB1, CTNND2, CUL3, CUL4B, CYBB, DCHS1, DCX, DDX3X, DICER1, DIP2A, DKC1, DLG2, DLG3, DMD, DMRT1, DNMT3A, DPP6, DSC2, DSCAM, DSG2, DSP, DYRK1A, EBP, EDA, EDNRB, EFNB1, EFTUD2, EHMT1, ELAVL2, ELN, EMX2, ENG, EP300, ERF, ERMARD, EXT1, EXT2, EYA1, EYA4, F8, F9, FANCB, FAS, FBN1, FGD1, FGF10, FGFR1, FLCN, FLG, FLNA, FMR1, FOXC1, FOXC2, FOXF1, FOXG1, FOXL2, FOXP1, FOXP2, FRMD7, FTSJ1, FZD4, GABRA1, GABRG2, GATA2, GATA3, GATA4, GATA6, GATAD2B, GCH1, GDF5, GDI1, GIGYF2, GJA5, GJA8, GK, GLA, GLI2, GLI3, GLMN, GNAS, GNB1, GPC3, GPHN, GRIA3, GRIN2A, GRIN2B, HCCS, HDAC4, HDAC8, HIST1H1E, HIVEP2, HIVEP3, HMGA2, HNF1B, HNRNPK, HNRNPU, HOXD13, HPRT1, IDS, IGF1R, IKBKG, IL1RAPL1, IQSEC2, IRF6, ITSN1, JAG1, KANSL1, KAT6A, KAT6B, KATNAL2, KCNH2, KCNQ1, KCNQ2, KDM5B, KDM5C, KDM6A, KDM6B, KIF11, KMT2A, KMT2B, KMT2C, KMT2D, L1CAM, LAMP2, LDLR, LEMD3, LHX4, LMNA, LMTK3, LMX1B, LRP5, MAGEL2, MAGT1, MAOA, MAP2K2, MBD5, MECP2, MED13L, MEF2C, MEIS2, MEN1, MID1, MITF, MLH1, MNX1, MSH2, MSH6, MSX2, MTAP, MTM1, MYBPC3, MYCN, MYH10, MYLK, MYT1L, NAA15, NBEA, NCKAP1, NDP, NEDD9, NEXMIF, NF1, NF2, NFIA, NHS, NIPBL, NKX2-5, NODAL, NR0B1, NR3C2, NR5A1, NRXN1, NSD1, NSDHL, NXF5, NYX, OCRL, OFD1, OPHN1, OTC, OTX2, PAFAH1B1, PAK2, PAK3, PAX2, PAX3, PAX6, PAX8, PAX9, PCDH19, PDHA1, PGK1, PHEX, PHF2, PHF21A, PHF3, PHF6, PHF8, PHIP, PIGA, PITX2, PKD1, PKD2, PKP2, PLP1, PMP22, PMS2, POGZ, POLR1D, PORCN, PQBP1, PRPS1, PTCH1, PTCHD1, PTEN, PTHLH, PTPN11, PURA, RAB39B, RAI1, RALGAPB, RASA1, RB1, RB1CC1, RET, RIMS1, RNF135, RP2, RPH3A, RPL15, RPS17, RPS19, RPS24, RPS26, RPS6KA3, RS1, RUNX1, SALL1, SALL4, SATB2, SCN1A, SCN2A, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SEMA3A, SETBP1, SETD1A, SETD2, SETD5, SF3B4, SGCE, SH2B1, SH2D1A, SHANK1, SHANK2, SHANK3, SHH, SHOX, SIM1, SIX3, SLC16A12, SLC16A2, SLC17A8, SLC2A1, SLC35A2, SLC4A10, SLC6A1, SLC6A8, SLC9A6, SMAD3, SMAD4, SMARCA4, SMARCB1, SMC1A, SMS, SNURF, SON, SOX10, SOX11, SOX2, SOX5, SOX9, SPAST, SPEN, SPINK1, SPRED1, SRCAP, SRY, STK11, STS, STXBP1, SYN1, SYNGAP1, SYP, TAB2, TAF13, TBL1XR1, TBR1, TBX1, TBX2, TBX20, TBX22, TBX3, TBX4, TBX5, TCF12, TCF20, TCF4, TCF7L2, TCOF1, TDGF1, TERT, TFAP2B, TGFBR1, TGFBR2, TGIF1, TIMM8A, TMLHE, TNNI3, TNRC6B, TP53, TP63, TRAPPC2, TRIO, TRIP12, TRPS1, TRRAP, TSC1, TSC2, TSPAN7, TWIST1, UBE2A, UBE3A, UBN2, UPF3B, USP9X, VEGFA, VHL, WAC, WDFY3, WDR45, WT1, XIAP, YAP1, YTHDC1, ZBTB18, ZC4H2, ZDHHC9, ZEB2, ZFPM2, ZIC1, ZIC2, ZIC3, ZIC4, ZMYND11, ZNF41, ZNF462, ZNF674, ZNF711 or ZWILCH. [029] In some embodiments, the expression of the target gene is decreased in the plurality of the modified population of cells in comparison to a population of cells contacted with any one of the vector, the viral particle, the population or the pharmaceutical composition, and a gRNA that does not specifically hybridize to the target nucleic acid sequence, but binds to the Cas-phi polypeptide to form a complex. In some embodiments, the expression of the target gene is decreased by at least about 1.10-fold, at least about 1.15-fold, at least about 1.20-fold, at least about 1.25-fold, at least about 1.30-fold, at least about 1.35-fold, at least about 1.40- fold, at least about 1.45-fold, at least about 1.50-fold, at least about 1.55-fold, at least about 1.60-fold, at least about 1.65-fold, at least about 1.70-fold, at least about 1.75-fold, at least about 1.80-fold, at least about 1.85-fold, at least about 1.90-fold, at least about 1.95-fold or at least about 2.0-fold. [030] In some embodiments, the target gene is MT-TL1, KCNQ2, DEAF1, SSBP1, KCNQ1, HNF1B, KAT6B, CDK8, MN1, COL4A1, CDKL5, VAPB, NALCN, TTR, RAC2, GJB2, MYO3A, MEIS2, BRCA2, NARS1, AIRE, GABRG3, RAD51, GATA6, PDX1, ETV6, BCL11B, CHEK2, WARS1, KAT6B, KCNQ1, PRNP, MAT1A, HCN4, DSG2, MAFB, ZSWIM6, WT1, NIPBL, COL9A3, MYH7, SMAD4, IL6ST, CAPN3, KCNK18, DDX3X, SCAMP5, APC, CEBPA, RBM20, PMS2, BEST1, HCN1, PKD1, MSH2, RAD50, EYA1, KCNQ2, PRKCE, SYT1, GNAS, GSDME, LMX1B, MECP2, LZTR1, KLHL7, SLC6A1, SUFU, CREBBP, KCNQ3, PPP2R1A, TOR1A, TGFBR1, COL5A1, SNAP25, GABBR2, SHANK3, PEX6, PPP2R5D, ATP1A3, KDM6A, TPM2, HNF4A, POLG, TUBB4A, PYGM, CPT2, BRCA1, LDLR, KCND2, NFKBIA, RPE65, PRPH2, BARD1, SDHD, PHKG2, MYL2, KCNK9, SPTB, TGFBR2, SSBP1, ATL1, CSF1R, SLC25A4, KAT6A, SATB2, POU3F3, SHOX, ENG, NOVA2, OTX2, PACS1, FBXO38, ALDH18A1, KCNC1, AARS1, CDKN2A, BBS7, PAX2, GNAO1, COL12A1, BLM, POGZ, TRPV4, FLG, FGFR1, KIF2A, ERF, EBF3, BRAF, RET, PDHA1, SPTAN1, PALB2, FASLG, TBC1D24, NOTCH3, FBN1, COL2A1, RRM2B, GLRA1, BMPR1A, MLH1, TCF3, THRB, CACNA1A, PKD2, ACVRL1, KIF5A, GLI3, KCNH1, GRIN2D, SHOC2, TP53, NTRK2, SPTLC1, GUCY2D, TPM1, CDH1, SPAST, NSD1, WFS1, PDE4D, PBX1, CBL, PMP22, DIAPH1, DMPK, GCK, KCNH2, TPP1, FANCC, FAS, BBS2, ABCC8, F11, KCNC3, MFN2, MPZ, CLCN1, PPP2CA, KCNJ2, SDHB, SPTBN2, CAPZA2, KLF1, NFIX, IFNGR1, COL1A2, MAPK8IP3, SCN5A, SRCAP, TP63, KCNA2, CDK13, CASQ2, TNNT1, DNM1L, SALL1, RHOA, KIF1A, RYR1, STAT3, HNF1A, COL7A1, PIK3CA, MYBPC3, CTCF, PTPN11, ATM, DEAF1, KCNT2, HMBS, ITPR1, TM4SF20, ASXL2, COL4A4, ADAR, DES, SCN2A, SLC4A1, HNF1B, BRIP1, FOXP1, KCNA1, MCCC1, BMPR2, MSH6, KRT9, MUTYH, RAF1, FH, ATAD3A, CASR, LMNA, REEP1, VHL, GATA2, DHDDS, ARID1A, NF1, RAD51C, KCNQ4, TNNT2, CXCR4, RYR2, ALPL, TPM3, SMN1, SERPINF1, PCGF2, SURF1, ATAD1, PTEN, TNFRSF11A, JAG1, ATP7B, CACNA1C, SLC16A2, SALL4, GJB6, MORC2, STING1, CHRNA4, TECPR2, GNA11, HEXB, HOGA1, DONSON, RRAS2, SLC6A8, SH3BP2, GNAQ, FLNA, PPP1CB, BICD2, ARID1B, PRKG1, TYR, ANKRD26, PHOX2B, EPAS1, PIK3R1, AFF4, MTOR, SAMD9L, ALK, SAMD9, PAH, PIEZO1, SOS2, STING1, HGSNAT, ABL1, AKT1, PDGFRB, GAMT, SLC35A3, CAMK2G, ATAD1, SURF1, IGHMBP2, GARS1, GLUD1, FGFR2, SMN1, FGFR3, MEFV, IDH2, KCNT1, VWF, GRIK2, SLC12A3, MAP2K1, KIF21A, PTEN, COG4, STAT1, CARD11, PMP2, SERPINF1, SPOP, STIM1, LAMB3, NLRC4, ITGB3, PNPO, CLCN2, SCN11A, NLRP3, IDH1, RIT1, TRIO, ADCY5, DNM2, SCN1B, SLC26A2, SCN8A, ALG1, KCNJ11, CHRNA1, MAP2K2, IFIH1, ACAD9, PKP2, CACNA1C, ORC1, UBTF, C3, KRAS, FANCA, FGF12, TIA1, HOXD13, CHRNB2, PSEN2, ACADM, MPL, SCN1A, GLMN, NRAS, RARB, PRKAR1A, SOS1, PCGF2, CACNA1E, PIK3CD or F5. [031] In some embodiments, the population of cells is a eukaryotic population of cells, a mammalian population of cells, an insect population of cells, a human population of cells or a plant population of cells. [032] This disclosure also provides a modified population of cells produced by any one of the methods of the disclosure. [033] This disclosure provides a method of reducing or eliminating the expression of a gene product in a subject comprising introducing to a cell of a subject the vector, the viral particle, the population or the pharmaceutical composition of the disclosure. This disclosure also provides method for treating or alleviating a symptom of a gene product related disorder in a subject comprising the step of introducing to a cell of the subject the vector, the viral particle, the population or the pharmaceutical composition of the disclosure. In some embodiments, the subject is a human. [034] Any of the above aspects can be combined with any other aspect. [035] Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All documents cited herein, including any cross referenced or related patent or application is hereby incorporated herein by reference in its entirety for all purposes, unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with respect to any invention disclosed or claimed herein or that it alone, or in any combination with any other reference or references, teaches, suggests or discloses any such invention. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. Other features and advantages of the disclosure will be apparent from the following detailed description and claims. BRIEF DESCRIPTION OF THE DRAWINGS [036] FIGS.1A-1B shows a schematic representation of the Cas-phi gene expression modulation system (“GEMS”). FIG.1A shows a gRNA with a targeting region (rectangle) that can hybridize to a target nucleic sequence adjacent to a PAM region. The gRNA is bound to a nuclease deficient Cas-phi polypeptide (oval). The three RuvC domains of the Cas-phi polypeptide are shown (three circles with missing slices). FIG.1B shows a schematic representation of a gRNA with a targeting region. The inclusion of two SapI restriction enzyme sites flanking the unique targeting region in the gRNA scaffold enables efficient swapping of genome-targeting guides. [037] FIG.2A shows a schematic representation of the Cas-phi constructs of the disclosure. Three Cas-phi orthologs (Cas-phi-1, Cas-phi-2 and Cas-phi-3) were each used to create three nuclease deficient Cas-phi polypeptide mutant constructs, respectively. (Cas-phi-1 - GEMS 1.1, GEMS 1.2, GEMS 1.3; Cas-phi-2 - GEMS 2.1; GEMS 2.2; GEMS 2.3; Cas-phi-3 - GEMS 3.1, GEMS 3.2, GEMS 3.3). Activator domains (VP64) were fused to the N-terminal and C-terminal region of each mutant. Various combinations of RuvC domain point mutations, RuvC-III domain deletions and zinc ribbon domain deletions were designed to total nine constructs, representing the minimal Cas-phi protein required to direct upregulation of gene expression. Aspartic acid to alanine mutations in the first RuvC domain have been shown to eliminate nuclease activity. Additional mutations were included to ensure complete nuclease removal. N-terminus 3xFLAG domains are included (not shown) for protein detection via Western blot or immunohistochemistry. [038] FIG.2B shows a sequence alignment of exemplary Cas-phi-2 polypeptides of the disclosure compared to a wildtype Cas-phi-2 polypeptide sequence. Wildtypd “Cas-phi-2” polypeptide (SEQ ID NO: 4) was aligned with three mutant Cas-phi-2 polypeptides: “GEMS_2.1” (SEQ ID NO: 83); “GEMS_2.2” (SEQ ID NO: 85); and “GEMS_2.3” (SEQ ID NO: 87). [039] FIG.2C shows a sequence alignment of exemplary Cas-phi-3 polypeptide of the disclosure compared to a wildtype Cas-phi-3 polypeptide sequence. Wildtype “Cas-phi-3” polypeptide (SEQ ID NO: 6) was aligned with three mutant Cas-phi-3 polypeptides: “GEMS_2.1” (SEQ ID NO: 89); “GEMS_2.2” (SEQ ID NO: 91); and “GEMS_2.3” (SEQ ID NO: 93). [040] FIGS.3A-3B are a series of graphs showing that GEMS upregulates STXBP1 expression in HEK293T cells. STXBP1 mRNA levels were detected using qPCR. FIG.3A shows the results using nuclease deficient Cas-phi-2 polypeptides (2.1, 2.2 and 2.3) each bound with one of two different gRNAs (g4, g5). FIG.3B shows the results using nuclease deficient Cas-phi-3 polypeptides (3.1, 3.2 and 3.3) each bound with one of two different gRNAs (g1, g5). Expression was normalized to housekeeping gene beta-actin (ACTB) or glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Fold change was determined by comparing to a non-targeting control guide for each respective construct (i.e., GEMS 2.1 uses its own GEMS 2.1 non-targeting control and so forth). Error bars represent standard deviation. [041] FIGS.4A-4B are a series of graphs showing that GEMS upregulates SYNGAP1 expression in Kelly neuroblastoma cells. SYNGAP1 mRNA levels detected using qPCR. FIG.4A shows the results using nuclease deficient Cas-phi-2 polypeptides (2.1 and 2.2) each bound to one of two different gRNAs (g1, g2). FIG.4B shows the results using nuclease deficient Cas-phi-3 polypeptides (3.1 and 3.2) with one gRNAs (g3). Expression was normalized to housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Fold change was determined by comparing to a non-targeting control guide for each respective construct. Error bars represent standard deviation. [042] FIGS.5A-5B are a series of graphs showing that GEMS upregulates ASCL1 in HEK293T cells. FIG.5A shows the results using nuclease deficient Cas-phi 3 polypeptide (3.1 and 3.3) with one gRNA (g1). ASCL1 mRNA levels detected using qPCR. Expression was normalized to housekeeping gene beta-actin (ACTB) or glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Fold change was determined by comparing to a non-targeting control guide for each respective construct. Error bars represent standard deviation. FIG.5B shows that a nuclease deficient Cas-phi-2 polypeptide (2.3) upregulates ASCL1 in HEK293T cells using two versions of the same gRNA. Two guides with identical sequences targeting ASCL1 that vary in length by 3 bases, where guide 1 (g1) is 23 bases and guide 4 (g4) is 20 bases. ASCL1 mRNA levels detected using qPCR. Expression was normalized to housekeeping gene beta-actin (ACTB) or glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Fold change was determined by comparing to a non-targeting control guide for each respective construct. Error bars represent standard deviation. [043] FIGS.6A-6B are a series of graphs showing that GEMS2.1 and GEMS3.1 upregulate luciferase expression via the SYNGAP1 promoter in HEK293T cells. Relative luminescence was measured using a plate reader. Luminescence signal from luciferase was normalized to an internal control (Renilla). Fold change was determined by comparing luminance from experimental conditions to the luminance of a non-targeting control guide for each respective construct. The gRNA comprised the mature scaffold (Table 6.2) in all samples. Each GEMS variant comprised the NLS linker 1 (SEQ ID NO: 297). [044] FIG.7 shows a schematic representation of the Cas-phi constructs of the disclosure. Cas-phi orthologs (Cas-phi-2 and Cas-phi-3) were each used to create five nuclease deficient Cas-phi polypeptide mutant constructs, respectively. (Cas-phi-2 - GEMS 2.4A, GEMS 2.4N, GEMS 2.5, GEMS 2.6A, GEMS2.6N; Cas-phi-3 - GEMS 3.4A, GEMS 3.4N, GEMS 3.5, GEMS 3.6A, GEMS3.6N). Activator domains (miniVPR) were fused to the C-terminal region of each mutant. Various combinations of RuvC domain point mutations were designed to total ten constructs, representing the minimal Cas-phi protein required to direct upregulation of gene expression. N-terminus 3xFLAG domains are included (not shown) for protein detection via Western blot or immunohistochemistry. [045] FIG.8 is a graph showing GEMS 2.0 variant with only a C-terminal VP64 upregulates SYNGAP1 expression using SYNGAPg7 gRNA in Kelly neuroblastoma cells. SYNGAP1 mRNA levels detected using qPCR. Expression was normalized to housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Fold change was determined by comparing to a non-targeting control guide for each respective construct. Error bars represent standard deviation. The gRNA comprised the mature scaffold (Table 6.2) in all samples. Each GEMS variant comprised the NLS linker 2 (SEQ ID NO: 298). [046] FIG.9 is a graph showing GEMS 3.1 and 3.4N variants with only a C-terminal VP64 upregulate SYNGAP1 expression using SYNGAPg7 gRNA in HEK293T cells. SYNGAP1 mRNA levels detected using qPCR. Expression was normalized to housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Fold change was determined by comparing to a non-targeting control guide for each respective construct. Error bars represent standard deviation. The gRNA comprised the mature scaffold (Table 6.2) in all samples. Each GEMS variant comprised the NLS linker 2 (SEQ ID NO: 298). [047] FIG.10 is a graph showing GEMS 3.1 variant with miniVPR upregulates SYNGAP1 expression using SYNGAPg7 gRNA in HEK293T cells. SYNGAP1 mRNA levels detected using qPCR. Expression was normalized to housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Fold change was determined by comparing to a non-targeting control guide for each respective construct. Error bars represent standard deviation. The gRNA comprised the mature scaffold (Table 6.2) in all samples. Each GEMS variant comprised the NLS linker 3 (SEQ ID NO: 299). [048] FIGS.11A-11B are a series of graphs showing that GEMS 2.0 and 3.0 variants with miniVPR upregulate IL1RN in HeLa cells. IL1RN mRNA levels detected using qPCR. Expression was normalized to housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Fold change was determined by comparing to a non-targeting control guide for each respective construct. Error bars represent standard deviation. The gRNA comprised the mature scaffold (Table 6.2) in all samples. Each GEMS variant comprised the NLS linker 3 (SEQ ID NO: 299). DETAILED DESCRIPTION OF THE INVENTION [049] This disclosure provides engineered CRISPR-Cas effector proteins (e.g., Cas-phi) that comprise at least one modification compared to an unmodified CRISPR-Cas effector protein, which preserves binding of the of the CRISPR complex to the target binding site and reduces or eliminates the nuclease activity of the CRISPR-Cas effector protein relative to a wildtype. In some embodiments, the engineered CRISPR-Cas effector protein is a nuclease deficient Cas-phi polypeptide. [050] This disclosure also provides nuclease deficient Cas-phi polypeptides that are fused with an effector domain (e.g., an activator or a repressor protein) at the N-terminus or the C- terminus, or both the N-terminus and the C-terminus to create a gene expression modulation system (“GEMS”). Fusion proteins with nuclease deficient Cas-phi polypeptides shuttle transcriptional activators or repressors to specific genomic loci, which is advantageous for highly specific and potent activation or silencing of target genes, without editing the genome or creating any DNA strand breaks. [051] This disclosure also provides viral vectors (e.g., AAV vectors) for delivery of CRISPR-Cas effector proteins, including nuclease deficient Cas-phi polypeptides. The clinical standard for many CRISPR-based therapeutics is Cas9 from S. aureus. The size of the smallest Cas9 is 3.1kb, which represents two-thirds of the total 4.7kb packaging capacity for AAV vectors. Therefore, a substantial benefit is to be gained by reducing the size of the DNA targeting module (DTM) used for therapeutic purposes. Shorter DTMs allow the opportunity to include additional effector domains (e.g., activator or repressor proteins) that can be packaged within the total 4.7kb packaging capacity for AAV vectors. This disclosure provides DTMs (i.e., nuclease deficient Cas-phi polypeptide) that is about 2.2kb to about 2.7kb in size, which is smaller than a wildtype Cas-phi polypeptide and also smaller than the smallest wildtype Cas9. This is advantageous for AAV packaging and the ability to include additional effector domains, which is beneficial for downstream therapeutic purposes. [052] The present invention in particular relates to methods for improving CRISPR-Cas systems, such as CRISPR-Cas system based therapy or therapeutics for modulating gene expression. Key characteristics of successful CRISPR-Cas systems, such as CRISPR-Cas system based therapy or therapeutics involve altered gene expression (increased or decreased relative to wildtype), high specificity, high efficacy, and high safety. [053] Definitions [054] Unless otherwise noted, the terms used herein have definitions as ordinarily used in the art. Some terms are defined below, and additional definitions can be found within the rest of the detailed description. [055] The term “a” or “an” refers to one or more of that entity, i.e., can refer to plural referents. As such, the terms “a,” “an,” “one or more,” and “at least one” are used interchangeably herein. In addition, reference to “an element” by the indefinite article “a” or “an” does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there is one and only one of the elements. [056] Unless otherwise stated or otherwise evident from the context, the term “about” means within 10% above or below the reported numerical value (except where such number would exceed 100% of a possible value or go below 0%). When used in conjunction with a range or series of values, the term “about” applies to the endpoints of the range or each of the values enumerated in the series, unless otherwise indicated. As used in this application, the terms “about” and “approximately” are used as equivalents. [057] In some embodiments the compositions herein comprise or the methods herein comprise delivering one or more components of a nuclei acid-targeting system. In general, “nucleic acid-targeting system” as used in the present application refers collectively to transcripts and other elements involved in the expression of or directing the activity of nucleic acid-targeting CRISPR-associated (“Cas”) genes (also referred to herein as an effector protein), including sequences encoding a nucleic acid-targeting Cas (effector) protein and a guide RNA, or other sequences and transcripts from a nucleic acid-targeting CRISPR locus. [058] In some embodiments, one or more elements of a nucleic acid-targeting system is derived from a particular organism comprising an endogenous nucleic acid-targeting CRISPR system. In general, a nucleic acid-targeting system is characterized by elements that promote the formation of a nucleic acid-targeting complex at the site of a target sequence. In the context of formation of a nucleic acid-targeting complex, “target sequence” refers to a sequence to which a guide sequence is designed to have complementarity, where hybridization between a target sequence and a guide RNA promotes the formation of a DNA or RNA-targeting complex. Full complementarity is not necessarily required, provided there is sufficient complementarity to cause hybridization and promote formation of a nucleic acid- targeting complex. A target sequence may comprise RNA polynucleotides. In some embodiments, a target sequence is located in the nucleus or cytoplasm of a cell. In some embodiments, the target sequence may be within an organelle of a eukaryotic cell, for example, mitochondrion or chloroplast. A sequence or template that may be used for recombination into the targeted locus comprising the target sequences is referred to as an “target nucleic acid sequence” or “target DNA” or “target sequence”. [059] Typically, in the context of an endogenous nucleic acid-targeting system, formation of a nucleic acid-targeting complex (comprising a guide RNA hybridized to a target sequence and complexed with one or more nucleic acid-targeting effector proteins) results in cleavage of one or both RNA strands in or near (e.g., within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or more base pairs from) the target sequence. In some embodiments, one or more vectors driving expression of one or more elements of a nucleic acid-targeting system are introduced into a host cell such that expression of the elements of the nucleic acid-targeting system direct formation of a nucleic acid-targeting complex at one or more target sites. For example, a nucleic acid-targeting effector protein and a guide RNA could each be operably linked to separate regulatory elements on separate vectors. Alternatively, two or more of the elements expressed from the same or different regulatory elements, may be combined in a single vector, with one or more additional vectors providing any components of the nucleic acid- targeting system not included in the first vector. Nucleic acid-targeting system elements that are combined in a single vector may be arranged in any suitable orientation, such as one element located 5′ with respect to (“upstream” of) or 3′ with respect to (“downstream” of) a second element. The coding sequence of one element may be located on the same or opposite strand of the coding sequence of a second element, and oriented in the same or opposite direction. In some embodiments, a single promoter drives expression of a transcript encoding a nucleic acid-targeting effector protein and a guide RNA embedded within one or more intron sequences (e.g., each in a different intron, two or more in at least one intron, or all in a single intron). In some embodiments, the nucleic acid-targeting effector protein and guide RNA are operably linked to and expressed from the same promoter. [060] In general, a CRISPR system is characterized by elements that promote the formation of a CRISPR complex at the site of a target sequence (also referred to as a protospacer in the context of an endogenous CRISPR system). In the context of formation of a CRISPR complex, “target sequence” refers to a sequence to which a guide sequence is designed to target, e.g., have complementarity, where hybridization between a target sequence and a guide sequence promotes the formation of a CRISPR complex. The section of the guide sequence through which complementarity to the target sequence is important for cleavage activity is referred to herein as the seed sequence. A target sequence may comprise any polynucleotide, such as DNA or RNA polynucleotides and is comprised within a target locus of interest. In some embodiments, a target sequence is located in the nucleus or cytoplasm of a cell. [061] In some embodiments, the nucleic acid-targeting effector protein is part of a fusion protein comprising one or more heterologous protein domains (e.g., about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more domains in addition to the nucleic acid-targeting effector protein). In some embodiments, the CRISPR effector protein is part of a fusion protein comprising one or more heterologous protein domains (e.g., about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more domains in addition to the CRISPR enzyme). [062] As used herein, the term “fuse,” or “fused” refers to the covalent linkage between two polypeptides in a fusion protein. The polypeptides may be fused via a peptide bond, either directly to each other or via a linker. The term “fusion protein” refers to a protein having at least two polypeptides covalently linked, either directly or via a linker (e.g., an amino acid linker). The polypeptides forming a fusion protein may be linked C-terminus to N-terminus, C-terminus to C-terminus, N-terminus to N-terminus, or N-terminus to C-terminus. The polypeptides of the fusion protein may be in any order and may include more than one of either or both of the constituent polypeptides. The term “fusion protein” encompass conservatively modified variants, polymorphic variants, alleles, mutants, subsequences, interspecies homologs, and immunogenic fragments of the antigens that make up the fusion protein. A fusion protein may be a protein developed from a fusion gene that is created through a joining of two or more genes originally coding for separate proteins. Translation of this fusion gene may result in a single or multiple polypeptides with functional properties derived from each of the original proteins. Fusion proteins of the disclosure may also comprise additional copies of a component antigen or immunogenic fragment thereof. [063] A CRISPR enzyme fusion protein may comprise any additional protein sequence, and optionally a linker sequence between any two domains. Examples of protein domains that may be fused to a CRISPR enzyme include, without limitation, epitope tags, reporter gene sequences, and protein domains having one or more of the following activities: methylase activity, demethylase activity, transcription activation activity, transcription repression activity, transcription release factor activity, histone modification activity, RNA cleavage activity and nucleic acid binding activity. Non-limiting examples of epitope tags include histidine (His) tags, V5 tags, FLAG tags (e.g., DYKDHDGDYKDHDIDYKDDDDK (SEQ ID NO: 124), influenza hemagglutinin (HA) tags, Myc tags, VSV-G tags, and thioredoxin (Trx) tags. Examples of reporter genes include, but are not limited to, glutathione-S- transferase (GST), horseradish peroxidase (HRP), chloramphenicol acetyltransferase (CAT) beta-galactosidase, beta-glucuronidase, luciferase, green fluorescent protein (GFP), HcRed, DsRed, cyan fluorescent protein (CFP), yellow fluorescent protein (YFP), and autofluorescent proteins including blue fluorescent protein (BFP). A CRISPR enzyme may be fused to a gene sequence encoding a protein or a fragment of a protein that bind DNA molecules or bind other cellular molecules, including but not limited to maltose binding protein (MBP), S-tag, Lex A DNA binding domain (DBD) fusions, GAL4 DNA binding domain fusions, and herpes simplex virus (HSV) BP16 protein fusions. Additional domains that may form part of a fusion protein comprising a CRISPR enzyme are described in US20110059502, incorporated herein by reference. In some embodiments, a tagged CRISPR enzyme is used to identify the location of a target sequence. [064] In some embodiments, a CRISPR enzyme may form a component of an inducible system. The inducible nature of the system would allow for spatiotemporal control of gene editing or gene expression using a form of energy. The form of energy may include but is not limited to electromagnetic radiation, sound energy, chemical energy and thermal energy. Examples of inducible system include tetracycline inducible promoters (Tet-On or Tet-Off), small molecule two-hybrid transcription activations systems (FKBP, ABA, etc), or light inducible systems (Phytochrome, LOV domains, or cryptochrome). In one embodiment, the CRISPR enzyme may be a part of a Light Inducible Transcriptional Effector (LITE) to direct changes in transcriptional activity in a sequence-specific manner. The components of a light may include a CRISPR enzyme, a light-responsive cytochrome heterodimer (e.g. from Arabidopsis thaliana), and a transcriptional activation/repression domain. Further examples of inducible DNA binding proteins and methods for their use are provided in U.S. 61/736,465 and U.S.61/721,283 and WO 2014/018423 and U.S. Pat. Nos.8,889,418, 8,895,308, US20140186919, US20140242700, US20140273234, US20140335620, WO2014093635, which is hereby incorporated by reference in its entirety. [065] In some embodiments, a recombination template is also provided. A recombination template may be a component of another vector as described herein, contained in a separate vector, or provided as a separate polynucleotide. In some embodiments, a recombination template is designed to serve as a template in homologous recombination, such as within or near a target sequence nicked or cleaved by a nucleic acid-targeting effector protein as a part of a nucleic acid-targeting complex. [066] Accordingly, when referring to the CRISPR system herein, in some aspects or embodiments, the CRISPR system comprises (i) a CRISPR protein or a polynucleotide encoding a CRISPR effector protein and (ii) one or more polynucleotides engineered to: complex with the CRISPR protein to form a CRISPR complex; and to complex with the target sequence. [067] In some embodiments, the therapeutic is for delivery (or application or administration) to a eukaryotic cell, either in vivo or ex vivo. [068] In some embodiments, the CRISPR protein is a Cas-phi from Biggiephage. [069] In some embodiments, the CRISPR protein further comprises one or more nuclear localization sequences (NLSs) capable of driving the accumulation of the CRISPR protein to a detectible amount in the nucleus of the cell of the organism. [070] In some embodiments, the CRISPR protein comprises one or more mutations. [071] In some embodiments, the CRISPR protein has one or more mutations in a catalytic domain, and wherein the protein further comprises a functional domain. [072] In some embodiments, the CRISPR system is comprised within a delivery system, optionally: a vector system comprising one or more vectors, optionally wherein the vectors comprise one or more viral vectors, optionally wherein the one or more viral vectors comprise one or more lentiviral, adenoviral or adeno-associated viral (AAV) vectors; or a particle or lipid particle, optionally wherein the CRISPR protein is complexed with the polynucleotides to form the CRISPR complex. [073] In some embodiments, the system, complex or protein is for use in a method of modifying an organism or a non-human organism by manipulation of the expression of a gene encoded by a target sequence in a genomic locus of interest. [074] In some embodiments, the polynucleotides encoding the sequence encoding or providing the CRISPR system are delivered via liposomes, particles, cell penetrating peptides, exosomes, microvesicles, or a gene-gun. In some embodiments, a delivery system is included. In some embodiments, the delivery system comprises: a vector system comprising one or more vectors comprising the engineered polynucleotides and polynucleotide encoding the CRISPR protein, optionally wherein the vectors comprise one or more viral vectors, optionally wherein the one or more viral vectors comprise one or more lentiviral, adenoviral or adeno-associated viral (AAV) vectors; or a particle or lipid particle, containing the CRISPR system or the CRISPR complex. [075] In some embodiments, the CRISPR protein has one or more mutations in a catalytic domain, and wherein the enzyme further comprises a functional domain. [076] In some embodiments, a recombination/repair template is provided. [077] As used herein, the term “gRNA molecule” or “gRNA” refers to a guide RNA that is capable of targeting a CRISPR nuclease or a nuclease-deficient CRISPR-associated protein to a target nucleic acid. Depending on context, the term “gRNA molecule” refers to a guide ribonucleic acid or to a nucleic acid encoding a gRNA. [078] As used herein, the term “sequence identity” refers to the extent to which two optimally aligned polynucleotides or polypeptide sequences are invariant throughout a window of alignment of residues, e.g. nucleotides or amino acids. An “identity fraction” for aligned segments of a test sequence and a reference sequence is the number of identical residues which are shared by the two aligned sequences divided by the total number of residues in the reference sequence segment, i.e. the entire reference sequence or a smaller defined part of the reference sequence. “Percent identity” is the identity fraction times 100. Percentage identity can be calculated using the alignment program Clustal Omega, available at ebi.ac.uk/Tools/msa/clustalo using default parameters. See, Sievers et al., “Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega” (2011 October 11) Molecular Systems Biology 7:539. For the purposes of calculating identity to the sequence, extensions, such as tags, are not included. [079] As used herein, a regulatory sequence (e.g., a promoter) is considered to be “operatively linked” when it is in a functional location and orientation in relation to a nucleic acid sequence it regulates to control transcriptional initiation and/or expression of that sequence. [080] As used herein, the term “self-complementary” when referring to an AAV vector refers to an AAV vector comprising a nucleic acid (i.e., a DNA) that forms a dimeric inverted repeat molecule that spontaneously anneals, resulting in earlier and more robust transgene expression compared with conventional single-strand (ss) AAV genomes. See, e.g., McCarty, Molecular Therapy 16(10):1648-1656 (2008). Unlike conventional ssAAV, self- complementary AAV (scAAV) can bypass second-strand synthesis, the rate-limiting step for gene expression. Moreover, double-stranded scAAV is less prone to DNA degradation after viral transduction, thereby increasing the number of copies of stable episomes. [081] As used herein, the terms “treat,” “treating” or “treatment of” (and grammatical variations thereof) mean that the severity of the subject's condition is reduced, at least partially improved or stabilized and/or that some alleviation, mitigation, decrease or stabilization in at least one clinical symptom is achieved and/or there is a delay in the progression of the disease or disorder. [082] As used herein, the terms “prevent,” “preventing” and “prevention” (and grammatical variations thereof) refer to prevention and/or delay of the onset of a disease, disorder and/or a clinical symptom(s) in a subject and/or a reduction in the severity of the onset of the disease, disorder and/or clinical symptom(s) relative to what would occur in the absence of the compositions and/or methods described herein. The prevention can be complete, e.g., the total absence of the disease, disorder and/or clinical symptom(s). The prevention can also be partial, such that the occurrence of the disease, disorder and/or clinical symptom(s) in the subject and/or the severity of onset is less than what would occur in the absence of the compositions and/or methods described herein. [083] In some embodiments, a nucleic acid sequence provided herein is a nucleic acid sense strand (e.g., 5' to 3' strand), or in the context of a viral sequences a plus (+) strand. In some embodiments, a nucleic acid sequence is a nucleic acid antisense strand (e.g., 3' to 5' strand), or in the context of viral sequences a minus (-) strand. [084] As used herein, a “therapeutically effective amount” is the amount of a vector, viral particles, a population of viral particles or a pharmaceutical composition provided herein that is effective to treat or prevent a disease or disorder in a subject or to ameliorate a sign or symptom thereof. The “therapeutically effective amount” may vary depending, for example, on the disease and/or symptoms of the disease, severity of the disease and/or symptoms of the disease or disorder, the age, weight, and/or health of the patient to be treated, and the judgment of the prescribing physician. [085] As used herein the term “wildtype” is a term of the art understood by skilled persons and means the typical form of an organism, strain, protein, gene or characteristic as it occurs in nature as distinguished from mutant or variant forms. [086] CRISPR-Cas Systems [087] According to some aspects of the present disclosure, the methods may comprise delivering one or more components of a CRISPR-Cas system to a target locus. In some examples, a nucleic acid-targeting system may comprise one or more components of a CRISPR-Cas system. [088] In some embodiments, the present invention relates to methods for increasing the expression of a gene product encoded by a target sequence using a CRISPR-Cas system, such as CRISPR-Cas system based therapy or therapeutics. In some embodiments, the present invention relates to methods for decreasing the expression of a gene product encoded by a target sequence using a CRISPR-Cas system, such as CRISPR-Cas system based therapy or therapeutics. [089] In certain embodiments, the CRISPR-Cas system comprises a CRISPR effector as defined herein elsewhere. [090] The methods of the present invention in particular involve optimization of selected parameters or variables associated with the CRISPR-Cas system and/or its functionality, as described herein further elsewhere. Optimization of the CRISPR-Cas system in the methods as described herein may depend on the target(s), such as the therapeutic target or therapeutic targets, the mode or type of CRISPR-Cas system modulation, such as CRISPR-Cas system based therapeutic target(s) modulation, modification, or manipulation, as well as the delivery of the CRISPR-Cas system components. One or more targets may be selected, depending on the genotypic and/or phenotypic outcome. For instance, one or more therapeutic targets may be selected, depending on (genetic) disease etiology or the desired therapeutic outcome. The (therapeutic) target(s) may be a single gene, locus, or other genomic site, or may be multiple genes, loci or other genomic sites. As is known in the art, a single gene, locus, or other genomic site may be targeted more than once, such as by use of multiple gRNAs. [091] CRISPR-Cas system activity, such as CRISPR-Cas system design may involve target disruption, such as target mutation, such as leading to gene knockout. CRISPR-Cas system activity, such as CRISPR-Cas system design may involve replacement of particular target sites, such as leading to target correction. CISPR-Cas system design may involve removal of particular target sites, such as leading to target deletion. CRISPR-Cas system activity may involve modulation of target site functionality, such as target site activity or accessibility, leading for instance to (transcriptional and/or epigenetic) gene or genomic region activation or gene or genomic region silencing. The skilled person will understand that modulation of target site functionality may involve CRISPR effector mutation (such as for instance generation of a catalytically inactive CRISPR effector) and/or functionalization (such as for instance fusion of the CRISPR effector with a heterologous functional domain, such as a transcriptional activator or repressor), as described herein elsewhere. Example functional domains suitable for use in the embodiments disclosed herein are discussed in further detail below. [092] In the methods and systems of the present invention use is made of a CRISPR-Cas protein and corresponding guide molecule. In certain embodiments, said CRISPR-Cas protein Cas-phi. The CRISPR-Cas system does not require the generation of customized proteins to target specific sequences but rather a single Cas protein can be programmed by guide molecule to recognize a specific nucleic acid target, in other words the Cas enzyme protein can be recruited to a specific nucleic acid target locus of interest using said guide molecule. [093] Engineered CRISPR-Cas Systems [094] In general, CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats), also known as SPIDRs (SPacer Interspersed Direct Repeats), constitute a family of DNA loci that are usually specific to a particular bacterial species. The CRISPR locus comprises a distinct class of interspersed short sequence repeats (SSRs) that were recognized in E. coli (Ishino et al., J. Bacteriol., 169:5429-5433 [1987]; and Nakata et al., J. Bacteriol., 171:3553-3556 [1989]), and associated genes. Similar interspersed SSRs have been identified in Haloferax mediterranei, Streptococcus pyogenes, Anabaena, and Mycobacterium tuberculosis (See, Groenen et al., Mol. Microbiol., 10:1057-1065 [1993]; Hoe et al., Emerg. Infect. Dis., 5:254-263 [1999]; Masepohl et al., Biochim. Biophys. Acta 1307:26-30 [1996]; and Mojica et al., Mol. Microbiol., 17:85-93 [1995]). The CRISPR loci typically differ from other SSRs by the structure of the repeats, which have been termed short regularly spaced repeats (SRSRs) (Janssen et al., OMICS J. Integ. Biol., 6:23-33 [2002]; and Mojica et al., Mol. Microbiol., 36:244-246 [2000]). In general, the repeats are short elements that occur in clusters that are regularly spaced by unique intervening sequences with a substantially constant length (Mojica et al., [2000], supra). Although the repeat sequences are highly conserved between strains, the number of interspersed repeats and the sequences of the spacer regions typically differ from strain to strain (van Embden et al., J. Bacteriol., 182:2393-2401 [2000]). CRISPR loci have been identified in more than 40 prokaryotes (See e.g., Jansen et al., Mol. Microbiol., 43:1565-1575 [2002]; and Mojica et al., [2005]) including, but not limited to Aeropyrum, Pyrobaculum, Sulfolobus, Archaeoglobus, Halocarcula, Methanobacterium, Methanococcus, Methanosarcina, Methanopyrus, Pyrococcus, Picrophilus, Thermoplasma, Corynebacterium, Mycobacterium, Streptomyces, Aquifex, Porphyromonas, Chlorobium, Thermus, Bacillus, Listeria, Staphylococcus, Clostridium, Thermoanaerobacter, Mycoplasma, Fusobacterium, Azarcus, Chromobacterium, Neisseria, Nitrosomonas, Desulfovibrio, Geobacter, Myxococcus, Campylobacter, Wolinella, Acinetobacter, Erwinia, Escherichia, Legionella, Methylococcus, Pasteurella, Photobacterium, Salmonella, Xanthomonas, Yersinia, Treponema, and Thermotoga. [095] CRISPR-Cas Enzyme [096] The terms “CRISPR-Cas protein”, “CRISPR protein”, “Cas protein”, “Cas effector protein”, “CRISPR enzyme”, and “Cas enzyme” may be used interchangeably herein. In its unmodified form, a CRISPR-Cas protein is a catalytically active protein. This implies that upon formation of a nucleic acid-targeting complex (comprising a guide RNA hybridized to a target sequence one or both DNA strands in or near (e.g., within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or more base pairs from) the target sequence is modified (e.g. cleaved). As used herein the term “sequence(s) associated with a target locus of interest” refers to sequences near the vicinity of the target sequence (e.g. within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 50, or more base pairs from the target sequence, wherein the target sequence is comprised within a target locus of interest). The unmodified catalytically active Cas-phi protein targets and cleaves foreign genomes in bacterial cells. Unlike other compact Cas proteins that preferentially cut single-strantded DNA, Cas-phi is able to cut double-stranded DNA. [097] General Properties of Cas-phi (“CasΦ” or “Cas12j”) [098] The present invention encompasses the use of a Cas-phi polypeptide. Herein such Cas-phi polypeptides are also referred to as “CasΦ” or “Cas12j” polypeptide. Cas-phi is a family of Cas proteins encoded in the Biggiephage clade. Cas-phi has three RuvC domains (RuvC-I, RuvC-II and RuvC-III) and a zinc ribbon domain. Cas-phi contains a C-terminal RuvC domain with remote homology to that of the TnpB nuclease superfamily from which type V CRISPR-Cas proteins are thought to have evolved (Pausch et. Al., CRISPR-CasΦ from huge phages is a hypercompact genome editor, 2020). Cas-phi has a small size of ~70– 80 kDa, about half the size of the Cas9 and Cas12a. [099] Orthologs of Cas-phi [0100] The terms “orthologue” (also referred to as “ortholog” herein) and “homologue” (also referred to as “homolog” herein) are well known in the art. By means of further guidance, a “homologue” of a protein as used herein is a protein of the same species which performs the same or a similar function as the protein it is a homologue of. Homologous proteins may but need not be structurally related, or are only partially structurally related. An “orthologue” of a protein as used herein is a protein of a different species which performs the same or a similar function as the protein it is an orthologue of. Orthologous proteins may but need not be structurally related, or are only partially structurally related. Homologs and orthologs may be identified by homology modelling (see, e.g., Greer, Science vol.228 (1985) 1055, and Blundell et al. Eur J Biochem vol 172 (1988), 513) or “structural BLAST” (Dey F, Cliff Zhang Q, Petrey D, Honig B. Toward a “structural BLAST”: using structural relationships to infer function. Protein Sci.2013 April; 22(4):359-66. doi: 10.1002/pro.2225.). See also Shmakov et al. (2015) for application in the field of CRISPR-Cas loci. Homologous proteins may but need not be structurally related, or are only partially structurally related. [0101] In some embodiments, the Cas-phi polypeptide is derived from an organism from Biggiephage clade. [0102] In some embodiments, the amino acid sequence of the Cas-phi polypeptide corresponds to Cas-phi-1 (SEQ ID NO: 2), Cas-phi-2 (SEQ ID NO: 4; PDB: 7LYT, 7M5O, 7LYS) or Cas-phi-3 (SEQ ID NO: 6; PDB: 7ODF). Amino acid sequences of exemplary Cas- phi polypeptides of the disclosure and polynucleotide sequences encoding the Cas-phi polypeptides are shown in Table 1. [0103] Cas-phi-1 [0104] In some embodiments, the Cas-phi polypeptide has a sequence homology or sequence identity of at least 60%, more particularly at least 70%, such as at least 80%, more preferably at least 85%, even more preferably at least 90%, such as for instance at least 95%, with Cas- phi-1 polypeptide comprising the amino acid sequence of SEQ ID NO: 2. [0105] In some embodiments, the Cas-phi polypeptide comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the Cas-phi polypeptide comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 2. [0106] In some embodiments, the Cas-phi polypeptide is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Cas-phi polypeptide is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 1. [0107] Cas-phi-2 [0108] In some embodiments, the Cas-phi polypeptide has a sequence homology or sequence identity of at least 60%, more particularly at least 70%, such as at least 80%, more preferably at least 85%, even more preferably at least 90%, such as for instance at least 95%, with Cas- phi-2 polypeptide comprising the amino acid sequence of SEQ ID NO: 4. [0109] In some embodiments, the Cas-phi polypeptide comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 4. In some embodiments, the Cas-phi polypeptide comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 4. [0110] In some embodiments, the Cas-phi polypeptide is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the Cas-phi polypeptide is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 3. [0111] Cas-phi-3 [0112] In some embodiments, the Cas-phi polypeptide has a sequence homology or sequence identity of at least 60%, more particularly at least 70%, such as at least 80%, more preferably at least 85%, even more preferably at least 90%, such as for instance at least 95%, with Cas- phi-3 polypeptide comprising the amino acid sequence of SEQ ID NO: 6. [0113] In some embodiments, the Cas-phi polypeptide comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the Cas-phi polypeptide comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 6. [0114] In some embodiments, the Cas-phi polypeptide is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the Cas-phi polypeptide is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 5. [0115] The skilled person will understand that any one of the Cas-phi polypeptides includes truncated forms of the Cas-phi polypeptide, whereby the sequence identity is determined over the length of the truncated form. (RuvC-1 domain is shown in bold font; RuvC-II domain is shown in underline, italicized font; RuvC-III domain is shown in underline font; zinc ribbon domain is shown in bold, italicized font; point mutations are shown in bold, underline font). [0116] Table 1. Exemplary Wildtype Cas-phi polypeptide sequences [0117] Modified Cas-phi polypeptides [0118] The disclosure provides a Cas-phi polypeptide that is mutated with respect to a corresponding wild-type enzyme, such that the mutated CRISPR-Cas protein lacks the ability to cleave one or both DNA strands of a target locus containing a target sequence. In particular embodiments, one or more nuclease domains of the Cas-phi polypeptide are mutated to produce a mutated Cas-phi polypeptide that is nuclease deficient. In particular embodiments, one or more RuvC domains of the Cas-phi polypeptide are mutated to produce a mutated Cas-phi polypeptide that is nuclease deficient. In some embodiments, one or more RuvC domains of the Cas-phi polypeptide are deleted to produce a truncated Cas-phi polypeptide that is nuclease deficient. In some embodiments, one or more zinc ribbon domains are deleted to produce a mutated Cas-phi polypeptide that is nuclease deficient. [0119] Cas-phi Point Mutations [0120] In particular embodiments, the Cas-phi polypeptide may be mutated with respect to a corresponding wild-type enzyme such that the mutated Cas-phi polypeptide lacks substantially all DNA cleavage activity. In some embodiments, the Cas-phi polypeptide is engineered and comprises at least one mutation that reduces or eliminates nuclease activity. [0121] In some embodiments, a Cas-phi polypeptide may be considered to substantially lack all DNA and/or RNA cleavage activity when the cleavage activity of the mutated enzyme is about no more than 25%, 10%, 5%, 1%, 0.1%, 0.01%, or less of the nucleic acid cleavage activity of the non-mutated form of the enzyme; an example can be when the nucleic acid cleavage activity of the mutated form is nil or negligible as compared with the non-mutated form. Where the Cas-phi polypeptide has nuclease activity, the Cas-phi polypeptide may be modified to have diminished nuclease activity e.g., nuclease inactivation of at least 70%, at least 80%, at least 90%, at least 95%, at least 97%, or 100% as compared with the wild type enzyme; or to put in another way, a Cas-phi enzyme having advantageously about 0% of the nuclease activity of the non-mutated or wild type Cas-phi enzyme or CRISPR enzyme, or no more than about 3% or about 5% or about 10% of the nuclease activity of the non-mutated or wild type Cas-phi enzyme. [0122] In these embodiments, the Cas-phi polypeptide is used as a generic DNA binding protein (or “DNA binding module” or “DTM”). The mutations may be artificially introduced mutations or gain- or loss-of-function mutations. [0123] In addition to the mutations described above, the CRISPR-Cas protein may be additionally modified. As used herein, the term “modified” with regard to a CRISPR-Cas protein generally refers to a CRISPR-Cas protein having one or more modifications or mutations (including point mutations, truncations, insertions, deletions, chimeras, fusion proteins, etc.) compared to the wild type Cas protein from which it is derived. By derived is meant that the derived enzyme is largely based, in the sense of having a high degree of sequence homology with, a wildtype enzyme, but that it has been mutated (modified) in some way as known in the art or as described herein. [0124] The additional modifications and/or truncations of the CRISPR-Cas protein may or may not cause an altered functionality. By means of example, and in particular with reference to CRISPR-Cas protein, modifications which do not result in an altered functionality include for instance codon optimization for expression into a particular host, or providing the nuclease with a particular marker (e.g. for visualization). Modifications with may result in altered functionality may also include mutations, including point mutations, insertions, deletions, truncations (including split nucleases), etc. [0125] In some embodiments, the Cas-phi polypeptide comprises a mutation of at least one residue, including but not limited to positions E107, Q127, D134, D141, K145, N195, K265, K278, D329, N333, D337, T340, D342, T357, K367, K371, K373, Q397, E446, N497, K522, K527, K528, E569, Q368, K642, I665, E674, A682, N693, N702, T709, E717 or E718 numbered according to Cas-phi-2 polypeptide (SEQ ID NO: 4) or any corresponding ortholog. In some embodiments, the Cas-phi polypeptide comprises a mutation of at least one residue, including but not limited to E107R, Q127R, D134R, D141R, K145R, N195R, K265R, K278R, D329R, N333R, D337R, T340R, D342R, T357R, K367R, K371R, K373R, Q397R, E446R, N497R, K522R, K527R, K528R, E569R, Q368R, K642R, I665R, E674R, A682R, N693R, N702R, T709R, E717R or E718R, numbered according to Cas-phi-2 polypeptide (SEQ ID NO: 4) or any corresponding ortholog. In some embodiments, the Cas- phi polypeptide comprises a mutation of E107R/E606Q, E107R/E606Q, Q127R/E606Q, Q127R/E606Q, D134R/E606Q, D134R/E606Q, D141R/E606Q, D141R/E606Q, K145R/E606Q, K145R/E606Q, N195R/E606Q, N195R/E606Q, K265R/E606Q, K265R/E606Q, K278R/E606Q, K278R/E606Q, D329R/E606Q, D329R/E606Q, N333R/E606Q, N333R/E606Q, D337R/E606Q, D337R/E606Q, T340R/E606Q, T340R/E606Q, D342R/E606Q, D342R/E606Q, T357R/E606Q, T357R/E606Q, K367R/E606Q, K367R/E606Q, K371R/E606Q, K371R/E606Q, K373R/E606Q, K373R/E606Q, D394R/E606Q, D394R/E606Q, Q397R/E606Q, Q397R/E606Q, E446R/E606Q, E446R/E606Q, N497R/E606Q, N497R/E606Q, K522R/E606Q, K522R/E606Q, K527R/E606Q, K527R/E606Q, K528R/E606Q, K528R/E606Q, E569R/E606Q, E569R/E606Q, Q368R/E606Q, Q368R/E606Q, K642R/E606Q, K642R/E606Q, I665R/E606Q, I665R/E606Q, E674R/E606Q, E674R/E606Q, A682R/E606Q, A682R/E606Q, N693R/E606Q, N693R/E606Q, D695R/E606Q, D695R/E606Q, N702R/E606Q, N702R/E606Q, T709R/E606Q, T709R/E606Q, E717R/E606Q, E717R/E606Q, E718R/E606Q, E718R/E606Q, D394R/D695A, D394R/D695A, E107R/D695A, E107R/D695A, Q127R/D695A, Q127R/D695A, D134R/D695A, D134R/D695A, D141R/D695A, D141R/D695A, K145R/D695A, K145R/D695A, N195R/D695A, N195R/D695A, K278R/D695A, K278R/D695A, D329R/D695A, D329R/D695A, N333R/D695A, N333R/D695A, D337R/D695A, D337R/D695A, T340R/D695A, T340R/D695A, T357R/D695A, T357R/D695A, K367R/D695A, K367R/D695A, K373R/D695A, K373R/D695A, Q397R/D695A or Q397R/D695A, numbered according to Cas-phi-2 polypeptide (SEQ ID NO: 4) or any corresponding ortholog. [0126] In certain embodiments, the Cas-phi polypeptide has reduced or no catalytic and/or nuclease activity. Cas-phi polypeptide mutations may include but are not limited to one or more mutations in the catalytic RuvC domain (e.g. RuvC-I, RuvC-II or RuvC-III). In some embodiments, the Cas-phi polypeptide comprises at least one mutation in the RuvC-I domain, the RuvC-II domain, the RuvC-III domain or a combination thereof. In some embodiments, the Cas-phi polypeptide comprises at least one mutation in the RuvC-I domain. In some embodiments, the Cas-phi polypeptide comprises at least one mutation in the RuvC-I domain and the RuvC-II domain. In some embodiments, the Cas-phi polypeptide comprises at least one mutation in the RuvC-I domain, the RuvC-II domain and the RuvC-III domain. [0127] Exemplary RuvC domains are shown in Table 2. [0128] Table 2. Cas-phi polypeptide RuvC and Zinc Ribbon Domains [0129] In some embodiments, the Cas-phi polypeptide comprises a mutation of at least one residue in at least one Ruv-C domain, including but not limited to positions D371, numbered according to Cas-phi-1 polypeptide (SEQ ID NO: 2) or any corresponding ortholog. In some embodiments, the Cas-phi polypeptide comprises a mutation of at least one residue in at least one Ruv-C domain, including but not limited to D371A numbered according to Cas-phi-1 polypeptide (SEQ ID NO: 2) or any corresponding ortholog. [0130] In some embodiments, the Cas-phi polypeptide comprises a mutation of at least one residue in at least one Ruv-C domain, including but not limited to positions D394, E606 and D695 numbered according to Cas-phi-2 polypeptide (SEQ ID NO: 4) or any corresponding ortholog. In some embodiments, the Cas-phi polypeptide comprises a mutation of at least one residue in at least one Ruv-C domain, including but not limited to D394A, D394N, D394R, E606A, E606Q, E606R, D695N, D695R and D695A numbered according to Cas-phi-2 polypeptide (SEQ ID NO: 4) or any corresponding ortholog. In some embodiments, the Cas- phi polypeptide comprises a mutation of D394A; D394A and E606A; D394A and D695A; D394A, E606A and D695A; or D394R, E606R and D695R, numbered according to Cas-phi- 2 polypeptide (SEQ ID NO: 4) or any corresponding ortholog. [0131] In some embodiments, the Cas-phi polypeptide comprises a mutation of at least one residue in at least one Ruv-C domain, including but not limited to positions D413, E618 and D708 numbered according to Cas-phi-3 polypeptide (SEQ ID NO: 6) or any corresponding ortholog. In some embodiments, the Cas-phi polypeptide comprises a mutation of at least one residue in at least one Ruv-C domain, including but not limited to D413A, D413N, E618A, E618Q, D708N and D708A numbered according to Cas-phi-3 polypeptide (SEQ ID NO: 6) or any corresponding ortholog. In some embodiments, the Cas-phi polypeptide comprises a mutation of D413A; D413A and E618A; D413A and D708A; or D413A, E618A and D708A, numbered according to Cas-phi-3 polypeptide (SEQ ID NO: 6) or any corresponding ortholog. [0132] In some embodiments, the Cas-phi polypeptide comprises a deletion of at least one RuvC domain according to a Cas-phi-1 polypeptide, a Cas-phi-2 polypeptide, a Cas-phi-3 polypeptide or any corresponding ortholog. Cas-phi polypeptide deletions may include but are not limited to one or more deletions in the catalytic RuvC domain (e.g. RuvC-I, RuvC-II or RuvC-III). In some embodiments, the Cas-phi polypeptide comprises at least one deletion in the RuvC-I domain, the RuvC-II domain, the RuvC-III domain or a combination thereof. In some embodiments, the Cas-phi polypeptide comprises a deletion of the RuvC-III domain. In some embodiments, the Cas-phi polypeptide comprises a deletion of the RuvC-II and RuvC-III domain. [0133] In some embodiments, the Cas-phi polypeptide comprises a deletion of at least one zinc ribbon domain according to a Cas-phi-1 polypeptide, a Cas-phi-2 polypeptide, a Cas-phi- 3 polypeptide or any corresponding ortholog. [0134] Amino acid sequences of exemplary mutant Cas-phi polypeptides and polynucleotide sequences encoding the same are shown in Table 3.1 and 3.2. (RuvC-I domain is shown in bold font, RuvC-II domain is shown in underline, italicized font, RuvC-III domain is shown in underline font, zinc ribbon domain is shown in bold, italicized font, point mutations are shown in bold, underline font, activator/repressor domains are shown in bold, italicized, underline font, nuclear localization sequence is shown in italicized font, tags are shown in double-underline font). [0135] Table 3.1. Exemplary mutant Cas-phi polypeptides [0136] Table 3.2. Exemplary mutant Cas-phi polypeptides PADRERLGDTKKPRVARSRKTMKRKDISNSTVEAMVTA [0137] In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.1” or “1.1”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.1” or “1.1”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 77. [0138] In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.1” or “1.1”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.1” or “1.1”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 76. [0139] In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.2” or “1.2”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.2” or “1.2”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 79. [0140] In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.2” or “1.2”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.2” or “1.2”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 78. [0141] In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.3” or “1.3”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 81. In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.3” or “1.3”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 81. [0142] In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.3” or “1.3”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 80. In some embodiments, the Cas-phi-1 mutant polypeptide (“CAS-PHI 1.3” or “1.3”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 80. [0143] In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.1” or “2.1”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 83. In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.1” or “2.1”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 83. [0144] In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.1” or “2.1”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 82. In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.1” or “2.1”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 82. [0145] In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.2” or “2.2”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 85. In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.2” or “2.2”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 85. [0146] In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.2” or “2.2”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 84. In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.2” or “2.2”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 84. [0147] In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.3” or “2.3”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 87. In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.3” or “2.3”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 87. [0148] In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.3” or “2.3”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 86. In some embodiments, the Cas-phi-2 mutant polypeptide (“CAS-PHI 2.3” or “2.3”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 86. [0149] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.4A” or “2.4A”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 160. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.4A” or “2.4A”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 160. [0150] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.4A” or “2.4A”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 159. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.4A” or “2.4A”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 159. [0151] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.4N” or “2.4N”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 162. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.4N” or “2.4N”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 162. [0152] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.4N” or “2.4N”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 161. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.4N” or “2.4N”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 161. [0153] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.5” or “2.5”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 164. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.5” or “2.5”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 164. [0154] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.5” or “2.5”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 163. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.5” or “2.5”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 163. [0155] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.6A” or “2.6A”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 166. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.6A” or “2.6A”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 166. [0156] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.6A” or “2.6A”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 165. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.6A” or “2.6A”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 165. [0157] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.6N” or “2.6N”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 168. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.6N” or “2.6N”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 168. [0158] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.6N” or “2.6N”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 167. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.6N” or “2.6N”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 167. [0159] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.7” or “2.7”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.7” or “2.7”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 170. [0160] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.7” or “2.7”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 169. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.7” or “2.7”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 169. [0161] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.8” or “2.8”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.8” or “2.8”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 172. [0162] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.8” or “2.8”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 171. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.8” or “2.8”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 171. [0163] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.9” or “2.9”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 174. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.9” or “2.9”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 174. [0164] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.9” or “2.9”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 173. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.9” or “2.9”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 173. [0165] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.11” or “2.11”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 176. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.11” or “2.11”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 176. [0166] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.11” or “2.11”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 175. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.11” or “2.11”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 175. [0167] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.12” or “2.12”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 178. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.12” or “2.12”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 178. [0168] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.12” or “2.12”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 177. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.12” or “2.12”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 177. [0169] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.13” or “2.13”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 180. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.13” or “2.13”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 180. [0170] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.13” or “2.13”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 179. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.13” or “2.13”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 179. [0171] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.14” or “2.14”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 182. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.14” or “2.14”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 182. [0172] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.14” or “2.14”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 181. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.14” or “2.14”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 181. [0173] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.15” or “2.15”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 184. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.15” or “2.15”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 184. [0174] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.15” or “2.15”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 183. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.15” or “2.15”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 183. [0175] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.16” or “2.16”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 186. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.16” or “2.16”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 186. [0176] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.16” or “2.16”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 185. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.16” or “2.16”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 185. [0177] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.17” or “2.17”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 188. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.17” or “2.17”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 188. [0178] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.17” or “2.17”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 187. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.17” or “2.17”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 187. [0179] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.18” or “2.18”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 190. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.18” or “2.18”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 190. [0180] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.18” or “2.18”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 189. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.18” or “2.18”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 189. [0181] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.19” or “2.19”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 192. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.19” or “2.19”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 192. [0182] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.19” or “2.19”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 191. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.19” or “2.19”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 191. [0183] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.21” or “2.21”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 194. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.21” or “2.21”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 194. [0184] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.21” or “2.21”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 193. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.21” or “2.21”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 193. [0185] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.22” or “2.22”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 196. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.22” or “2.22”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 196. [0186] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.22” or “2.22”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 195. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.22” or “2.22”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 195. [0187] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.23” or “2.23”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 198. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.23” or “2.23”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 198. [0188] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.23” or “2.23”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 197. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.23” or “2.23”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 197. [0189] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.24” or “2.24”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 200. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.24” or “2.24”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 200. [0190] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.24” or “2.24”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 199. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.24” or “2.24”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 199. [0191] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.25” or “2.25”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 202. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.25” or “2.25”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 202. [0192] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.25” or “2.25”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 201. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.25” or “2.25”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 201. [0193] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.26” or “2.26”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 204. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.26” or “2.26”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 204. [0194] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.26” or “2.26”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 203. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.26” or “2.26”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 203. [0195] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.27” or “2.27”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 206. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.27” or “2.27”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 206. [0196] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.27” or “2.27”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 205. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.27” or “2.27”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 205. [0197] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.28” or “2.28”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 208. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.28” or “2.28”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 208. [0198] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.28” or “2.28”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 207. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.28” or “2.28”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 207. [0199] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.29” or “2.29”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 210. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.29” or “2.29”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 210. [0200] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.29” or “2.29”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 209. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.29” or “2.29”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 209. [0201] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.31” or “2.31”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 212. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.31” or “2.31”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 212. [0202] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.31” or “2.31”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 211. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.31” or “2.31”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 211. [0203] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.32” or “2.32”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 214. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.32” or “2.32”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 214. [0204] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.32” or “2.32”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 213. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.32” or “2.32”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 213. [0205] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.33” or “2.33”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 216. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.33” or “2.33”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 216. [0206] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.33” or “2.33”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 215. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.33” or “2.33”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 215. [0207] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.34” or “2.34”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 218. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.34” or “2.34”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 218. [0208] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.34” or “2.34”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 217. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.34” or “2.34”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 217. [0209] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.35” or “2.35”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 220. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.35” or “2.35”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 220. [0210] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.35” or “2.35”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 219. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.35” or “2.35”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 219. [0211] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.36” or “2.36”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 222. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.36” or “2.36”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 222. [0212] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.36” or “2.36”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 221. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.36” or “2.36”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 221. [0213] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.37” or “2.37”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 224. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.37” or “2.37”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 224. [0214] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.37” or “2.37”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 223. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.37” or “2.37”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 223. [0215] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.38” or “2.38”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 226. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.38” or “2.38”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 226. [0216] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.38” or “2.38”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 225. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.38” or “2.38”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 225. [0217] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.39” or “2.39”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 228. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.39” or “2.39”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 228. [0218] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.39” or “2.39”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 227. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.39” or “2.39”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 227. [0219] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.41” or “2.41”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 230. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.41” or “2.41”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 230. [0220] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.41” or “2.41”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 229. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.41” or “2.41”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 229. [0221] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.42” or “2.42”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 232. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.42” or “2.42”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 232. [0222] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.42” or “2.42”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 231. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.42” or “2.42”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 231. [0223] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.43” or “2.43”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 234. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.43” or “2.43”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 234. [0224] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.43” or “2.43”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 233. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.43” or “2.43”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 233. [0225] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.44” or “2.44”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 236. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.44” or “2.44”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 236. [0226] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.44” or “2.44”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 235. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.44” or “2.44”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 235. [0227] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.45” or “2.45”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 238. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.45” or “2.45”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 238. [0228] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.45” or “2.45”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 237. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.45” or “2.45”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 237. [0229] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.46” or “2.46”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 240. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.46” or “2.46”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 240. [0230] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.46” or “2.46”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 239. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.46” or “2.46”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 239. [0231] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.47” or “2.47”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 242. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.47” or “2.47”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 242. [0232] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.47” or “2.47”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 241. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.47” or “2.47”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 241. [0233] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.48” or “2.48”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 244. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.48” or “2.48”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 244. [0234] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.48” or “2.48”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 243. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.48” or “2.48”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 243. [0235] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.49” or “2.49”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 246. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.49” or “2.49”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 246. [0236] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.49” or “2.49”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 245. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.49” or “2.49”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 245. [0237] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.51” or “2.51”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 248. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.51” or “2.51”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 248. [0238] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.51” or “2.51”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 247. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.51” or “2.51”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 247. [0239] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.52” or “2.52”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 250. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.52” or “2.52”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 250. [0240] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.52” or “2.52”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 249. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.52” or “2.52”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 249. [0241] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.53” or “2.53”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 252. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.53” or “2.53”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 252. [0242] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.53” or “2.53”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 251. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.53” or “2.53”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 251. [0243] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.54” or “2.54”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 254. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.54” or “2.54”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 254. [0244] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.54” or “2.54”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 253. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.54” or “2.54”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 253. [0245] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.55” or “2.55”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 256. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.55” or “2.55”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 256. [0246] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.55” or “2.55”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 255. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.55” or “2.55”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 255. [0247] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.56” or “2.56”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 258. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.56” or “2.56”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 258. [0248] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.56” or “2.56”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 257. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.56” or “2.56”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 257. [0249] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.57” or “2.57”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 260. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.57” or “2.57”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 260. [0250] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.57” or “2.57”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 259. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.57” or “2.57”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 259. [0251] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.58” or “2.58”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 262. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.58” or “2.58”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 262. [0252] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.58” or “2.58”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 261. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.58” or “2.58”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 261. [0253] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.59” or “2.59”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 264. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.59” or “2.59”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 264. [0254] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.59” or “2.59”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 263. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.59” or “2.59”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 263. [0255] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.61” or “2.61”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 266. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.61” or “2.61”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 266. [0256] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.61” or “2.61”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 265. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.61” or “2.61”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 265. [0257] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.62” or “2.62”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 268. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.62” or “2.62”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 268. [0258] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.62” or “2.62”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 267. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.62” or “2.62”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 267. [0259] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.63” or “2.63”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 270. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.63” or “2.63”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 270. [0260] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.63” or “2.63”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 269. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.63” or “2.63”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 269. [0261] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.64” or “2.64”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 272. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.64” or “2.64”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 272. [0262] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.64” or “2.64”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 271. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.64” or “2.64”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 271. [0263] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.65” or “2.65”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 274. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.65” or “2.65”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 274. [0264] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.65” or “2.65”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 273. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.65” or “2.65”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 273. [0265] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.66” or “2.66”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 276. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.66” or “2.66”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 276. [0266] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.66” or “2.66”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 275. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.66” or “2.66”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 275. [0267] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.67” or “2.67”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 278. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.67” or “2.67”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 278. [0268] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.67” or “2.67”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 277. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.67” or “2.67”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 277. [0269] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.68” or “2.68”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 280. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “2.68” or “2.68”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 280. [0270] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.68” or “2.68”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 279. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “2.68” or “2.68”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 279. [0271] In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.1” or “3.1”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 89. In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.1” or “3.1”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 89. [0272] In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.1” or “3.1”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 88. In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.1” or “3.1”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 88. [0273] In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.2” or “3.2”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 91. In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.2” or “3.2”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 91. [0274] In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.2” or “3.2”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 90. In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.2” or “3.2”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 90. [0275] In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.3” or “3.3”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.3” or “3.3”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 93. [0276] In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.3” or “3.3”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 92. In some embodiments, the Cas-phi-3 mutant polypeptide (“CAS-PHI 3.3” or “3.3”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 92. [0277] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.4A” or “3.4A”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 282. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.4A” or “3.4A”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 282. [0278] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.4A” or “3.4A”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 281. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.4A” or “3.4A”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 281. [0279] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.4N” or “3.4N”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 284. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.4N” or “3.4N”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 284. [0280] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.4N” or “3.4N”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 283. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.4N” or “3.4N”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 283. [0281] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.5” or “3.5”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 286. In some embodiments, the Cas-phi- 2 mutant polypeptide (CAS-PHI “3.5” or “3.5”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 286. [0282] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.5” or “3.5”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 285. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.5” or “3.5”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 285. [0283] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.6A” or “3.6A”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 288. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.6A” or “3.6A”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 288. [0284] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.6A” or “3.6A”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 287. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.6A” or “3.6A”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 287. [0285] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.6N” or “3.6N”) comprises, consists essentially of or consists of an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 290. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.6N” or “3.6N”) comprises, consists essentially of or consists of the amino acid sequence of SEQ ID NO: 290. [0286] In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.6N” or “3.6N”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to the amino acid sequence of SEQ ID NO: 289. In some embodiments, the Cas-phi-2 mutant polypeptide (CAS-PHI “3.6N” or “3.6N”) is encoded by a polynucleotide sequence comprising, consisting essentially of or consisting of a nucleic acid sequence of SEQ ID NO: 289. Exemplary Cas-Phi Fusion Polypeptides [0287] Fusion proteins may without limitation include for instance fusions with heterologous domains or functional domains (e.g., localization signals, catalytic domains, etc.). In certain embodiments, various different modifications may be combined (e.g., a mutated nuclease which is catalytically inactive and which further is fused to a functional domain, such as for instance to induce DNA methylation or another nucleic acid modification, such as including without limitation a break (e.g. by a different nuclease (domain)), a mutation, a deletion, an insertion, a replacement, a ligation, a digestion, a break or a recombination). [0288] As used herein, “altered functionality” includes without limitation an altered specificity (e.g., altered target recognition, increased (e.g., “enhanced” Cas proteins) or decreased specificity, or altered PAM recognition), altered activity (e.g., increased or decreased catalytic activity, including catalytically inactive nucleases or nickases), and/or altered stability (e.g., fusions with destabilization domains). Suitable heterologous domains include without limitation a nuclease, a ligase, a repair protein, a methyltransferase, (viral) integrase, a recombinase, a transposase, an argonaute, a cytidine deaminase, a retron, a group II intron, a phosphatase, a phosphorylase, a sulpfurylase, a kinase, a polymerase, an exonuclease, etc. Examples of all these modifications are known in the art. It will be understood that a “modified” nuclease as referred to herein, and in particular a “modified” Cas or “modified” CRISPR-Cas system or complex preferably still has the capacity to interact with or bind to the polynucleic acid (e.g., in complex with the guide molecule). [0289] Linkers [0290] In some embodiments, the Cas-phi polypeptide may have associated (e.g., via fusion protein or suitable linkers) one or more functional domains, including for example, one or more domains from the group comprising, consisting essentially of, or consisting of deaminase activity, methylase activity, demethylase activity, transcription activation activity, transcription repression activity, transcription release factor activity, histone modification activity, RNA cleavage activity, DNA cleavage activity, nucleic acid binding activity, and molecular switches (e.g., light inducible). [0291] Suitable linkers for use in the methods of the present invention are well known to those of skill in the art and include, but are not limited to, straight or branched-chain carbon linkers, heterocyclic carbon linkers, or peptide linkers. In particular embodiments, the linker is used to separate the Cas-phi polypeptide and the effector domain by a distance sufficient to ensure that each protein retains its required functional property. Preferred peptide linker sequences adopt a flexible extended conformation and do not exhibit a propensity for developing an ordered secondary structure. In certain embodiments, the linker can be a chemical moiety which can be monomeric, dimeric, multimeric or polymeric. Preferably, the linker comprises amino acids. Typical amino acids in flexible linkers include Gly, Asn and Ser. Accordingly, in particular embodiments, the linker comprises a combination of one or more of Gly, Asn and Ser amino acids. Other near neutral amino acids, such as Thr and Ala, also may be used in the linker sequence. Exemplary linkers are disclosed in Maratea et al. (1985), Gene 40: 39-46; Murphy et al. (1986) Proc. Nat'l. Acad. Sci. USA 83: 8258-62; U.S. Pat. Nos.4,935,233; and 4,751,180. For example, GlySer linkers GS, GGS, GGGS or GSG can be used. GGS, GSG, GGGS or GGGGS linkers can be used in repeats of 3 (such as (GGS)3 (SEQ ID NO: 146), (GGGGS)3 (SEQ ID NO: 94)) or 5 (SEQ ID NO: 95), 6 (SEQ ID NO: 96), 7 (SEQ ID NO: 97), 9 (SEQ ID NO: 98) or even 12 (SEQ ID NO: 99) or more, to provide suitable lengths. In some embodiments, the linker comprises (GGGGS)3 (SEQ ID NO: 94) (GGGGS)6 (SEQ ID NO: 96), (GGGGS)9 (SEQ ID NO: 98), (GGGGS)12 (SEQ ID NO: 99), (GGGGS)1 (SEQ ID NO: 147), (GGGGS)2 (SEQ ID NO: 100), (GGGGS)4 (SEQ ID NO: 101), (GGGGS)5 (SEQ ID NO: 102), (GGGGS)7 (SEQ ID NO: 103), (GGGGS)8 (SEQ ID NO: 104), (GGGGS)10 (SEQ ID NO: 105), or (GGGGS)11 (SEQ ID NO: 106). In some embodiments, the linker comprises LEPGEKPYKCPECGKSFSQSGALTRHQRTHTR (SEQ ID NO: 107). In some embodiments, the linker comprises GSEASGSGRA (SEQ ID NO: 290) In some embodiments, the linker comprises an XTEN linker. [0292] NLSs [0293] In some embodiments, the Cas-phi polypeptide further comprises one or more nuclear localization sequences (NLSs), such as about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs. In some embodiments, vector comprises one or more NLSs not naturally present in the Cpf1 effector protein. In some embodiments, the NLS is present in the vector 5′ and/or 3′ of the Cpf1 effector protein sequence In some embodiments, the RNA-targeting effector protein comprises about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the amino-terminus, about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the carboxy-terminus, or a combination of these (e.g., zero or at least one or more NLS at the amino-terminus and zero or at one or more NLS at the carboxy terminus). When more than one NLS is present, each may be selected independently of the others, such that a single NLS may be present in more than one copy and/or in combination with one or more other NLSs present in one or more copies. In some embodiments, an NLS is considered near the N- or C-terminus when the nearest amino acid of the NLS is within about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50, or more amino acids along the polypeptide chain from the N- or C- terminus. Non-limiting examples of NLSs include an NLS sequence derived from: the NLS of the SV40 virus large T-antigen, having the amino acid sequence PKKKRKV (SEQ ID NO: 108); the NLS from nucleoplasmin (e.g., the nucleoplasmin bipartite NLS with the sequence KRPAATKKAGQAKKKK (SEQ ID NO: 109)); the c-myc NLS having the amino acid sequence PAAKRVKLD (SEQ ID NO: 110) or RQRRNELKRSP (SEQ ID NO: 111); the hRNPA1 M9 NLS having the sequence NQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGGY (SEQ ID NO: 112); the sequence RMRIZFKNKGKDTAELRRRRVEVSVELRKAKKDEQILKRRNV (SEQ ID NO: 113) of the IBB domain from importin-alpha; the sequences VSRKRPRP (SEQ ID NO: 114) and PPKKARED (SEQ ID NO: 115) of the myoma T protein; the sequence PQPKKKPL (SEQ ID NO: 116) of human p53; the sequence SALIKKKKKMAP (SEQ ID NO: 117) of mouse c-abl IV; the sequences DRLRR (SEQ ID NO: 118) and PKQKKRK (SEQ ID NO: 119) of the influenza virus NS1; the sequence RKLKKKIKKL (SEQ ID NO: 120) of the Hepatitis virus delta antigen; the sequence REKKKFLKRR (SEQ ID NO: 121) of the mouse Mxl protein; the sequence KRKGDEVDGVDEVAKKKSKK (SEQ ID NO: 122) of the human poly(ADP-ribose) polymerase; and the sequence RKCLQAGMNLEARKTKK (SEQ ID NO: 123) of the steroid hormone receptors (human) glucocorticoid. In general, the one or more NLSs are of sufficient strength to drive accumulation of the DNA/RNA-targeting Cas protein in a detectable amount in the nucleus of a eukaryotic cell. In general, strength of nuclear localization activity may derive from the number of NLSs in the nucleic acid- targeting effector protein, the particular NLS(s) used, or a combination of these factors. [0294] In some embodiments, the Cas-phi polypeptide further comprises one or more nuclear localization sequences fused with a linker (“NLS linker”). In some embodiments, an “NLS linker 1” comprises the amino acid sequence of KRPAATKKAGQAKKKKGS (SEQ ID NO: 297). In some embodiments, an “NLS linker 2” comprises the amino acid sequence of KRPAATKKAGQAKKKKGSEASGSGRA (SEQ ID NO: 298). In some embodiments, an “NLS linker 1” comprises the amino acid sequence of KRPAATKKAGQAKKKKGGGGSGGGGSGGGGS (SEQ ID NO: 299). [0295] In some instances, it is advantageous to position a nuclear localization signal sequence (NLS) at the N terminus. In some instances, it is advantageous to position the NLS at the C terminus. In some instances, it is advantageous to position the NLS at the N terminus and the C-terminus. In some embodiments, an N- and C-terminal nuclear localization signal sequence (NLSs) can also function as linker. [0296] Detection of accumulation in the nucleus may be performed by any suitable technique. For example, a detectable marker may be fused to the nucleic acid-targeting protein, such that location within a cell may be visualized, such as in combination with a means for detecting the location of the nucleus (e.g., a stain specific for the nucleus such as DAPI). Cell nuclei may also be isolated from cells, the contents of which may then be analyzed by any suitable process for detecting protein, such as immunohistochemistry, Western blot, or enzyme activity assay. Accumulation in the nucleus may also be determined indirectly, such as by an assay for the effect of nucleic acid-targeting complex formation (e.g., assay for DNA or RNA cleavage or mutation at the target sequence, or assay for altered gene expression activity affected by DNA or RNA-targeting complex formation and/or DNA or RNA-targeting Cas protein activity), as compared to a control not exposed to the nucleic acid-targeting Cas protein or nucleic acid-targeting complex, or exposed to a nucleic acid- targeting Cas protein lacking the one or more NLSs. [0297] Effector Domains [0298] When more than one effector domain is included, the effector domains may be the same or different. In general, the positioning of the one or more effector domain on the inactivated Cas-phi polypeptide is one which allows for correct spatial orientation for the effector domain to affect the target with the attributed functional effect. For example, if the effector domain is a transcription activator (e.g., VP64 or p65), the transcription activator is placed in a spatial orientation which allows it to affect the transcription of the target. Likewise, a transcription repressor will be advantageously positioned to affect the transcription of the target, and a nuclease (e.g., Fok1) will be advantageously positioned to cleave or partially cleave the target. This may include positions other than the N-/C-terminus of the CRISPR enzyme. [0299] In some embodiments, the effector domain is a transcription activator. In some embodiments, the effector domain is a transcription repressor. [0300] Exemplary transcription activators domains and repressor domains for use in the methods of the present invention are well known to those of skill in the art and include, but are not limited to those listed in Table 4. [0301] Table 4. Exemplary activator and repressor domains [0302] Exemplary fusion Cas-phi polypeptides include but are not limited to those listed in Table 5.1. (RuvC-I domain is shown in bold font, domain is shown in underline, italicized font, RuvC-III domain is shown in underline zinc ribbon domain is shown in bold, italicized font, point mutations are shown in bold, underline font, VP64 activator domains are shown in bold, italicized, underline font, nuclear localization sequence (NLS) or NLS-linker is shown in italicized font, 3X FLAG tags are shown in double- underline font). [0303] Table 5.1. Exemplary Fusion Cas-phi Polypeptides [0304] Exemplary fusion Cas-phi polypeptides include but are not limited to those listed in Table 5.2. (RuvC-I domain is shown in bold font, domain is shown in underline, italicized font, RuvC-III domain is shown in underline zinc ribbon domain is shown in bold, italicized font, point mutations are shown in bold, underline font, mini VPR activator domains are shown in bold, italicized, underline font, nuclear localization sequence(NLS) or NLS-linker is shown in italicized font, 3X FLAG epitope tags are shown in double-underline font). [0305] Table 5.2. Exemplary Fusion Cas-Phi Polypeptides [0306] Guide Molecules [0307] The CRISPR-Cas system may comprise one or more guide molecules. The guide molecule or guide RNA of a Class 2 type V CRISPR-Cas protein comprises a tracr-mate sequence (encompassing a “direct repeat” in the context of an endogenous CRISPR system) and a guide sequence (also referred to as a “spacer” in the context of an endogenous CRISPR system). In certain embodiments, the guide molecule may comprise, consist essentially of, or consist of a direct repeat sequence fused or linked to a guide sequence or spacer sequence. [0308] In general, a CRISPR system is characterized by elements that promote the formation of a CRISPR complex at the site of a target sequence. In the context of formation of a CRISPR complex, “target sequence” refers to a sequence to which a guide sequence is designed to have complementarity, where hybridization between a target RNA sequence and a guide sequence promotes the formation of a CRISPR complex. [0309] The terms “guide molecule”, “guide RNA”, “sgRNA” and “gRNA” are used interchangeably herein to refer to RNA-based molecules that are capable of forming a complex with a CRISPR-Cas protein and comprises a guide sequence having sufficient complementarity with a target nucleic acid sequence to hybridize with the target nucleic acid sequence and direct sequence-specific binding of the complex to the target nucleic acid sequence. The guide molecule or guide RNA specifically encompasses RNA-based molecules having one or more chemically modifications (e.g., by chemical linking two ribonucleotides or by replacement of one or more ribonucleotides with one or more deoxyribonucleotides), as described herein. [0310] Guide Sequence [0311] As used herein, the term “guide sequence” or “targeting sequence” in the context of a CRISPR-Cas system, comprises any polynucleotide sequence having sufficient complementarity with a target nucleic acid sequence to hybridize with the target nucleic acid sequence and direct sequence-specific binding of a nucleic acid-targeting complex to the target nucleic acid sequence. Optimal alignment may be determined with the use of any suitable algorithm for aligning sequences, non-limiting example of which include the Smith- Waterman algorithm, the Needleman-Wunsch algorithm, algorithms based on the Burrows- Wheeler Transform (e.g., the Burrows Wheeler Aligner), ClustalW, ClustalX, BLAT, Novoalign (Novocraft Technologies; available at www.novocraft.com), ELAND (Illumina, San Diego, Calif.), SOAP (available at soap.genomics.org.cn), and Maq (available at maq.sourceforge.net). In some embodiments, a guide sequence is about or more than about 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 75, or more nucleotides in length. In some embodiments, a guide sequence is less than about 75, 50, 45, 40, 35, 30, 25, 20, 15, 12, or fewer nucleotides in length. The ability of a guide sequence (within a nucleic acid-targeting guide RNA) to direct sequence-specific binding of a nucleic acid-targeting complex to a target nucleic acid sequence may be assessed by any suitable assay (as described in EP3009511 or US2016208243). For example, the components of a nucleic acid-targeting CRISPR system sufficient to form a nucleic acid-targeting complex, including the guide sequence to be tested, may be provided to a host cell having the corresponding target nucleic acid sequence, such as by transfection with vectors encoding the components of the nucleic acid-targeting complex, followed by an assessment of preferential targeting (e.g., cleavage) within or in the vicinity of the target nucleic acid sequence, such as by Surveyor assay as described herein. Similarly, cleavage of a target nucleic acid sequence (or a sequence in the vicinity thereof) may be evaluated in a test tube by providing the target nucleic acid sequence, components of a nucleic acid-targeting complex, including the guide sequence to be tested and a control guide sequence different from the test guide sequence, and comparing binding or rate of cleavage at or in the vicinity of the target sequence between the test and control guide sequence reactions. Other assays are possible, and will occur to those skilled in the art. A guide sequence, and hence a nucleic acid-targeting guide RNA may be selected to target any target nucleic acid sequence. [0312] In certain embodiments, the guide sequence or spacer length of the guide molecules is from 15 to 50 nt. In certain embodiments, the spacer length of the guide RNA is at least 15 nucleotides. In certain embodiments, the spacer length is from 15 to 17 nt, e.g., 15, 16, or 17 nt, from 17 to 20 nt, e.g., 17, 18, 19, or 20 nt, from 20 to 24 nt, e.g., 20, 21, 22, 23, or 24 nt, from 23 to 25 nt, e.g., 23, 24, or 25 nt, from 24 to 27 nt, e.g., 24, 25, 26, or 27 nt, from 27-30 nt, e.g., 27, 28, 29, or 30 nt, from 30-35 nt, e.g., 30, 31, 32, 33, 34, or 35 nt, or 35 nt or longer. In certain example embodiment, the guide sequence is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 3940, 41, 42, 43, 44, 45, 46, 47 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 nt. [0313] A guide sequence may be selected to target any target sequence. In some embodiments, the target sequence is a sequence within a gene transcript or mRNA. In some embodiments, the target sequence is a sequence within a genome of a cell. [0314] In some embodiments, the guide sequence is an RNA sequence of between 10 to 50 nt in length, but more particularly of about 20-30 nt advantageously about 20 nt, 23 nt, 24 nt or 25 nt in length. In some embodiments, the guide sequence is about 20 nt in length. [0315] Exemplary guide RNA spacer sequences (guide sequence) include but are not limited to those shown in Table 6.1. Exemplary Cas-phi sgRNA scaffold sequences are shown in Table 6.2. Any one of the sgRNA scaffold sequences of Table 6.2 can be combined with the guide RNA spacer sequences (guide sequences) of Table 6.1. [0316] Table 6.1. Guide sequences for STXBP1, SYNGAP, ASCL1, IL1RN and non- targeting controls. [0317] Table 6.2. Cas-phi sgRNA scaffold sequences [0318] In certain embodiments, the guide molecule comprises non-naturally occurring nucleic acids and/or non-naturally occurring nucleotides and/or nucleotide analogs, and/or chemically modifications. Preferably, these non-naturally occurring nucleic acids and non- naturally occurring nucleotides are located outside the guide sequence. Non-naturally occurring nucleic acids can include, for example, mixtures of naturally and non-naturally occurring nucleotides. Non-naturally occurring nucleotides and/or nucleotide analogs may be modified at the ribose, phosphate, and/or base moiety. In an embodiment of the invention, a guide nucleic acid comprises ribonucleotides and non-ribonucleotides. In one such embodiment, a guide comprises one or more ribonucleotides and one or more deoxyribonucleotides. In an embodiment of the invention, the guide comprises one or more non-naturally occurring nucleotide or nucleotide analog such as a nucleotide with phosphorothioate linkage, a locked nucleic acid (LNA) nucleotides comprising a methylene bridge between the 2′ and 4′ carbons of the ribose ring, or bridged nucleic acids (BNA). Other examples of modified nucleotides include 2′-O-methyl analogs, 2′-deoxy analogs, or 2′-fluoro analogs. Further examples of modified bases include, but are not limited to, 2-aminopurine, 5-bromo-uridine, pseudouridine, inosine, 7-methylguanosine. Examples of guide RNA chemical modifications include, without limitation, incorporation of 2′-O-methyl (M), 2′-O- methyl 3′phosphorothioate (MS), S-constrained ethyl(cEt), or 2′-O-methyl 3′thioPACE (MSP) at one or more terminal nucleotides. Such chemically modified guides can comprise increased stability and increased activity as compared to unmodified guides, though on-target vs. off-target specificity is not predictable. (See, Hendel, 2015, Nat Biotechnol.33(9):985-9, doi: 10.1038/nbt.3290, published online 29 Jun.2015 Ragdarm et al., 0215, PNAS, E7110- E7111; Allerson et al., J. Med. Chem.2005, 48:901-904; Bramsen et al., Front. Genet., 2012, 3:154; Deng et al., PNAS, 2015, 112:11870-11875; Sharma et al., MedChemComm., 2014, 5:1454-1471; Hendel et al., Nat. Biotechnol. (2015) 33(9): 985-989; Li et al., Nature Biomedical Engineering, 2017, 1, 0066 DOI:10.1038/s41551-017-0066). In some embodiments, the 5′ and/or 3′ end of a guide RNA is modified by a variety of functional moieties including fluorescent dyes, polyethylene glycol, cholesterol, proteins, or detection tags. (See Kelly et al., 2016, J. Biotech.233:74-83). In certain embodiments, a guide comprises ribonucleotides in a region that binds to a target RNA and one or more deoxyribonucletides and/or nucleotide analogs in a region that binds to Cas-phi. In some embodiments, the guide comprises a modified Cpf1 crRNA, having a 5′-handle and a guide segment further comprising a seed region and a 3′-terminus. In some embodiments, the modified guide can be used with a Cpf1 of any one of Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1); Francisella tularensis subsp. Novicida U112 Cpf1 (FnCpf1); L. bacterium MC2017 Cpf1 (Lb3Cpf1); Butyrivibrio proteoclasticus Cpf1 (BpCpf1); Parcubacteria bacterium GWC2011_GWC2_44_17 Cpf1 (PbCpf1); Peregrinibacteria bacterium GW2011_GWA_33_10 Cpf1 (PeCpf1); Leptospira inadai Cpf1 (LiCpf1); Smithella sp. SC_K08D17 Cpf1 (SsCpf1); L. bacterium MA2020 Cpf1 (Lb2Cpf1); Porphyromonas crevioricanis Cpf1 (PcCpf1); Porphyromonas macacae Cpf1 (PmCpf1); Candidatus Methanoplasma termitum Cpf1 (CMtCpf1); Eubacterium eligens Cpf1 (EeCpf1); Moraxella bovoculi 237 Cpf1 (MbCpf1); Prevotella disiens Cpf1 (PdCpf1); or L. bacterium ND2006 Cpf1 (LbCpf1). [0319] In certain embodiments, the target sequence may be associated with a PAM (protospacer adjacent motif) or PFS (protospacer flanking sequence or site); that is, a short sequence recognized by the CRISPR complex. Depending on the nature of the CRISPR-Cas protein, the target sequence should be selected such that its complementary sequence in the RNA duplex (also referred to herein as the non-target sequence) is upstream or downstream of the PAM. [0320] Further, engineering of the PAM Interacting (PI) domain may allow programing of PAM specificity, improve target site recognition fidelity, and increase the versatility of the CRISPR-Cas protein, for example as described for Cas9 in Kleinstiver et al. Nature.2015 Jul. 23; 523(7561):481-5. doi: 10.1038/nature14592. As further detailed herein, the skilled person will understand that Cas-phi proteins may be modified analogously. Vectors [0321] Provided herein are vectors for delivery of the engineered CRISPR-Cas effector proteins disclosed herein (e.g., nuclease deficient Cas-phi polypeptides) to host cells. Provided herein is a vector comprising: a nucleic acid sequence encoding a Cas-phi polypeptide disclosed herein and a polynucleotide sequence encoding a gRNA. [0322] In general, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. It is a replicon, such as a plasmid, viral expression cassette, phage, or cosmid, into which another DNA segment may be inserted so as to bring about the replication of the inserted segment. Generally, a vector is capable of replication when associated with the proper control elements. [0323] Vectors include, but are not limited to, nucleic acid molecules that are single- stranded, double-stranded, or partially double-stranded; nucleic acid molecules that comprise one or more free ends, or no free ends (e.g., circular); nucleic acid molecules that comprise DNA, RNA, or both; and other varieties of polynucleotides known in the art. One type of vector is a “plasmid,” which refers to a circular double stranded DNA loop into which additional DNA segments can be inserted, such as by standard molecular cloning techniques. Another type of vector is a viral vector, wherein virally-derived DNA or RNA sequences are present in the vector for packaging into a virus (e.g., retroviruses, replication defective retroviruses, adenoviruses, replication defective adenoviruses, and adeno-associated viruses (AAVs)). Viral vectors also include polynucleotides carried by a virus for transfection into a host cell. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as “expression vectors.” Vectors that are used for expression in a eukaryotic cell can be referred to herein as “eukaryotic expression vectors.” Common expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. [0324] In some embodiments, the vectors provided herein are plasmids or viral expression cassettes that comprise additional nucleic acid sequences. In some embodiments, the vectors provided herein may be used to generate recombinant virus particles to serve as viral vectors for gene delivery. In some embodiments, the vectors provided herein are formulated for use with via non-viral delivery systems. Further provided herein are plasmids comprising any of the vector nucleic acid sequences disclosed herein. [0325] Viral and non-viral based gene transfer methods can be used to introduce nucleic acids into mammalian cells or target tissues. Such methods can be used to administer nucleic acids sequences encoding engineered CRISPR-Cas effector proteins disclosed herein and/or gRNAs to cells in culture, or in a host organism. [0326] Viral vector delivery systems include DNA and RNA viruses, which have either episomal or integrated genomes after delivery to the cell. [0327] Non-viral vector delivery systems include DNA plasmids, RNA, naked nucleic acid, and nucleic acid complexed with a delivery vehicle, such as a liposome. Methods of non-viral delivery of nucleic acids include lipofection, nucleofection, microinjection, biolistics, exosomes, virosomes, liposomes, immunoliposomes, polycation or lipid:nucleic acid conjugates, naked DNA, artificial virions, and agent-enhanced uptake of DNA. Lipofection is described in e.g., US 5,049,386, US 4,946,787; and US 4,897,355. Some lipofection reagents are sold commercially (e.g., Transfectam™ and Lipofectin™). Cationic and neutral lipids that are suitable for efficient receptor-recognition lipofection of polynucleotides include those described in, for example, WO 91/17424; WO 91/16024. Delivery can be to cells (e.g. in vitro or ex vivo administration) or target tissues (e.g. in vivo administration). [0328] In some embodiments, a vector provided herein is non-integrating. In some embodiments, a vector provided herein is non-replicating. [0329] Recombinant expression vectors can comprise a nucleic acid sequence encoding a Cas-phi polypeptide disclosed herein (and a polynucleotide sequence encoding a gRNA) in a form suitable for expression of the nucleic acid sequence in a host cell, which means that the recombinant expression vectors include one or more regulatory elements. Such regulatory elements may be selected on the basis of the host cells to be used for expression and operatively linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operatively linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory element(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell). Advantageous vectors include lentiviruses and adeno-associated viruses, and specific types of such vectors can also be selected for targeting particular types of cells. [0330] As used herein, the term “regulatory element” includes promoters, enhancers, internal ribosomal entry sites (IRES), and other expression control elements (e.g., transcription termination signals, such as polyadenylation signals and poly-U sequences). Such regulatory elements are described, for example, in Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990). Regulatory elements include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). A tissue- specific promoter may direct expression primarily in a desired tissue of interest, such as muscle, neuron, bone, skin, blood, specific organs (e.g., liver, pancreas), or particular cell types (e.g., lymphocytes). Regulatory elements may also direct expression in a temporal- dependent manner, such as in a cell-cycle dependent or developmental stage-dependent manner, which may or may not also be tissue or cell-type specific. In some embodiments, a vector comprises one or more pol III promoter (e.g., 1, 2, 3, 4, 5, or more pol III promoters), one or more pol II promoters (e.g., 1, 2, 3, 4, 5, or more pol II promoters), one or more pol I promoters (e.g., 1, 2, 3, 4, 5, or more pol I promoters), or combinations thereof. Examples of pol III promoters include, but are not limited to, U6 and H1 promoters. Examples of pol II promoters include, but are not limited to, the retroviral Rous sarcoma virus (RSV) LTR promoter (optionally with the RSV enhancer), the cytomegalovirus (CMV) promoter (optionally with the CMV enhancer) [see, e.g., Boshart et al, Cell, 41:521-530 (1985)], the SV40 promoter, the dihydrofolate reductase promoter, the β-actin promoter, the phosphoglycerol kinase (PGK) promoter, and the EFa promoter. Also encompassed by the term “regulatory element” are enhancer elements, such as Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE); CMV enhancers; the R-U5′ segment in LTR of HTLV-I (Mol. Cell. Biol., Vol.8(1), p.466-472, 1988); SV40 enhancer; and the intron sequence between exons 2 and 3 of rabbit β-globin (Proc. Natl. Acad. Sci. USA., Vol. 78(3), p.1527-31, 1981). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression desired, etc. A vector can be introduced into host cells to thereby produce transcripts, proteins, or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., CRISPR transcripts, proteins, enzymes, mutant forms thereof, fusion proteins thereof, gRNAs, etc.). Exemplary promoters are disclosed in WO 2011/028929. [0331] In some embodiments, bicistronic vectors are used for expression of a gRNA and a Cas-phi polypeptide disclosed herein. In some embodiments, a vector comprises a CBh promoter. In some embodiments, a vector comprises an RNA polymerase III promoter, such as a U6 promoter. [0332] In some embodiments, a vector comprises a nucleic acid sequence encoding a Cas-phi polypeptide disclosed herein and a polynucleotide sequence encoding a gRNA, wherein the gRNA is operatively linked to a promoter recognized by RNA polymerase III. In some embodiments, the gRNA is operatively linked to a human U6 promoter. [0333] In some embodiments, a vector provided herein further comprises an artificial intron. In some embodiments, a vector provided herein further comprises a chimeric intron. [0334] In some embodiments, a vector provided herein further comprises or encodes a woodchuck hepatitis virus post-transcriptional element (WPRE). See, e.g., Wang and Verma, Proc. Natl. Acad. Sci., USA, 96: 3906-3910 (1999). In some embodiments, a vector comprises or encodes a hepatitis B virus posttranscriptional regulatory element (HBVPRE) and/or a RNA transport element (RTE). In some embodiments, the WPRE or HBVPRE sequence is any of the WPRE or HBVPRE sequences disclosed in US 6,136,597 or US 6,287,814. In some embodiments, a vector provided herein further comprises or encodes a WPRE3 or a wsl3 regulatory element. In some embodiments, a WPRE3 comprises or consists of GATAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGTT GC TCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCG TA TGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTAGTTCTTGCCACGGCGGAACTCA TC GCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTG GT GTT (SEQ ID NO: 144). [0335] In some embodiments, a vector provided herein further comprises or encodes a polyadenylation (polyA) signal sequence. As used herein, a “polyadenylation signal sequence” refers to a DNA sequence that when transcribed regulates the addition of a polyA tail to the mRNA transcript. In some embodiments, a polyA signal sequence is a SV40, human, bovine or rabbit polyA signal sequence. In some embodiments, a polyA signal sequence is a SV40 polyA signal sequence. In some embodiments, a polyA signal sequence is a β-globin polyA signal sequence. In some embodiments, a polyA signal sequence is a human growth hormone polyA signal sequence or a bovine growth hormone polyA signal sequence. In some embodiments, a SV40 polyA signal sequence comprises or consists of AACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACA AA TAAAGCATTTTTTTCACTGC (SEQ ID NO: 145). [0336] In some embodiments, a vector provided herein further comprises or encodes a Kozak sequence (for example, a DNA sequence transcribed to an RNA Kozak sequence). In some embodiments, a vector comprises a Kozak sequence upstream of the transgene. In some embodiments, the Kozak sequence is encoded by GCCACC. In some embodiments, the Kozak sequence (e.g., RNA Kozak sequence) comprises or consists of ACCAUGG, GCCGCCACCAUGG (SEQ ID NO: 141), CCACCAUG or CCACCAUGG. [0337] In some embodiments, a vector provided herein further comprises a TATA transcriptional regulatory activation site (see, e.g., Francois et al., (2005) J. Virol. 79(17):11082–11094). [0338] Vectors can be designed for expression of nucleic acid sequences disclosed herein in prokaryotic or eukaryotic cells. For example, nucleic acid sequences can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors), yeast cells, or mammalian cells. Suitable host cells are discussed further in Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990). Alternatively, a recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase. [0339] Vectors may be introduced and propagated in a prokaryote or prokaryotic cell. In some embodiments, a prokaryote is used to amplify copies of a vector to be introduced into a eukaryotic cell or as an intermediate vector in the production of a vector to be introduced into a eukaryotic cell (e.g., amplifying a plasmid as part of a viral vector packaging system). In some embodiments, a prokaryote is used to amplify copies of a vector and express one or more nucleic acids, such as to provide a source of one or more proteins for delivery to a host cell or host organism. Expression of proteins in prokaryotes is most often carried out in Escherichia coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, such as to the amino terminus of the recombinant protein. Such fusion vectors may serve one or more purposes, such as: (i) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Example fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988. Gene 67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein. Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and pET I1d (Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 60-89). In some embodiments, a vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSecl (Baldari et al., 1987. EMBO J.6: 229-234), pMFa (Kuijan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (Invitrogen Corp, San Diego, Calif.). In some embodiments, a vector drives protein expression in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., SF9 cells) include the pAc series (Smith, et al., 1983. Mol. Cell. Biol.3: 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170: 31-39). [0340] In some embodiments, a vector is capable of driving expression of one or more nucleic acid sequences in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al., 1987. EMBO J.6: 187-195). When used in mammalian cells, the expression vector's control functions are typically provided by one or more regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, simian virus 40, and others disclosed herein and known in the art. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook et al., Molecular Cloning: A Laboratory Manual.2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989. [0341] In some embodiments, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue- specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev.1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol.43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J.8: 729-733) and immunoglobulins (Baneiji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; US 4,873,316). Developmentally-regulated promoters are also encompassed, e.g., the murine Hox promoters (Kessel and Gruss, 1990. Science 249: 374- 379) and the α-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev.3: 537-546). [0342] In some embodiments, a host cell is transiently or non-transiently transfected with one or more vectors comprising one or more nucleic acid sequences disclosed herein. In some embodiments, a cell is transfected as it naturally occurs in a subject. In some embodiments, a cell that is transfected is taken from a subject. In some embodiments, the cell is derived from cells taken from a subject, such as a cell line. A wide variety of cell lines for tissue culture are known in the art and exemplified herein elsewhere. Cell lines are available from a variety of sources known to those with skill in the art (see, e.g., the American Type Culture Collection (ATCC) (Manassas, VA)). Examples of cell lines include, but are not limited to, C8161, CCRF-CEM, MOLT, mIMCD-3, NHDF, HeLa-S3, Huhl, Huh4, Huh7, HUVEC, HASMC, HEKn, HEKa, MiaPaCell, Panc, PC-3, TF1, CTLL-2, CIR, Rat6, CV1, RPTE, A10, T24, J82, A375, ARH-77, Calul, SW480, SW620, SKOV3, SK-UT, CaCo2, P388D1, SEM-K2, WEHI-231, HB56, TIB55, Jurkat, J45.01, LRMB, Bcl-1, BC-3, IC21, DLD2, Raw264.7, NRK, NRK-52E, MRC5, MEF, Hep G2, HeLa B, HeLa T4, COS, COS-1, COS-6, COS- M6A, BS-C-1 monkey kidney epithelial, BALB/3T3 mouse embryo fibroblast, 3T3 Swiss, 3T3-L1, 132-d5 human fetal fibroblasts; 10.1 mouse fibroblasts, 293-T, 3T3, 721, 9L, A2780, A2780ADR, A2780cis, A172, A20, A253, A431, A-549, ALC, B16, B35, BCP-1 cells, BEAS-2B, bEnd.3, BHK-21, BR 293, BxPC3, C3H-10T1/2, C6/36, Cal-27, CHO, CHO-7, CHO—IR, CHO-K1, CHO-K2, CHO-T, CHO Dhfr−/−, COR-L23, COR-L23/CPR, COR- L23/5010, COR-L23/R23, COS-7, COV-434, CML T1, CMT, CT26, D17, DH82, DU145, DuCaP, EL4, EM2, EM3, EMT6/AR1, EMT6/AR10.0, FM3, H1299, H69, HB54, HB55, HCA2, HEK-293, HeLa, Hepalclc7, HL-60, HMEC, HT-29, Jurkat, JY cells, K562 cells, Ku812, KCL22, KG1, KYOl, LNCap, Ma-Mel 1-48, MC-38, MCF-7, MCF-10A, MDA-MB- 231, MDA-MB-468, MDA-MB-435, MDCK II, MDCK II, MOR/0.2R, MONO-MAC 6, MTD-1A, MyEnd, NCI-H69/CPR, NCI-H69/LX10, NCI-H69/LX20, NCI-H69/LX4, NIH- 3T3, NALM-1, NW-145, OPCN/OPCT cell lines, Peer, PNT-1A/PNT 2, RenCa, RIN-5F, RMA/RMAS, Saos-2 cells, Sf-9, SkBr3, T2, T-47D, T84, THP1 cell line, U373, U87, U937, VCaP, Vero cells, WM39, WT-49, X63, YAC-1, YAR, and transgenic varieties thereof. In some embodiments, a cell transfected with one or more vectors comprising one or more nucleic acid sequences disclosed herein is used to establish a new cell line comprising one or more vector-derived sequences. [0343] In some embodiments, a vector provided herein is a viral vector. In some embodiments, a viral vector is a retrovirus, lentivirus, adenovirus, adeno-associated virus (AAV) or herpes simplex virus (HSV) vector. Retroviral vectors include those based upon murine leukemia virus (MuLV), gibbon ape leukemia virus (GaLV), Simian immunodeficiency virus (SIV), human immunodeficiency virus (HIV), and combinations thereof (see, e.g., Buchscher et al., J. Virol.66:2731-2739 (1992); Johann et al., J. Virol. 66:1635-1640 (1992); Sommnerfelt et al., Virol.176:58-59 (1990); Wilson et al., J. Virol. 63:2374-2378 (1989); Miller et al., J. Virol.65:2220-2224 (1991)). [0344] In some embodiments, a viral vector is an adeno-associated virus (AAV) vector. In some embodiments, an AAV vector comprises a first AAV inverted terminal repeat (ITR) located upstream of the promoter polynucleotide sequence and a second AAV ITR located downstream of the transgene polynucleotide sequence. ITRs are sequences that mediate AAV proviral integration and packaging of AAV DNA into virions. In some embodiments, an AAV vector comprises a first AAV ITR and a second AAV ITR flanking the polynucleotide sequences to be packaged into a recombinant AAV (rAAV) particle. In some embodiments, the first AAV ITR is an AAV2 ITR and the second AAV ITR is an AAV2 ITR. AAV expression cassettes and related plasmids provided herein can be used in production of rAAV particles. [0345] In some embodiments, an AAV vector provided herein is self-complementary. In some embodiments, an AAV vector provided herein is single-stranded. [0346] Further provided herein is a viral particle (also referred to as a virion) comprising any of the vectors, expression cassettes or nucleic acid molecules provided herein. In some embodiments, a viral particle is a retrovirus, lentivirus, adenovirus, AAV or HSV particle. In some embodiments the viral particle is a recombinant AAV (rAAV) particle. In some embodiments, the rAAV particle is an AAV1, AAV2, AAV3 (including types 3A and 3B), AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAVrh32.33, AAVrh.8, AAVrh.10, AAVrh32.33, AAVrh.74, AAVhu.68, avian AAV, bovine AAV, canine AAV, equine AAV, ovine AAV, snake AAV, bearded dragon AAV, AAV2i8, AAV2g9, AAV-LK03, AAV7m8, AAV Anc80, TM-AAV6, AAV-PHP.A, AAV- PHP.B, AAV-PHP.S, AAV-PHPeB, AAV-DJ, AAV-CAP.B10, AAV2-r3.45, AAV2-LSS, AAV2PFG, AAV2-PPS, AAV2-TLH or AAV2-GMN serotype particle. In some embodiments, the rAAV particle comprises an AAV1, AAV2, AAV3 (including types 3A and 3B), AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAVrh32.33, AAVrh.8, AAVrh.10, AAVrh32.33, AAVrh.74, AAVhu.68, avian AAV, bovine AAV, canine AAV, equine AAV, ovine AAV, snake AAV, bearded dragon AAV, AAV2i8, AAV2g9, AAV-LK03, AAV7m8, AAV Anc80, TM-AAV6, AAV-PHP.A, AAV- PHP.B, AAV-PHP.S, AAV-PHPeB, AAV-DJ, AAV-CAP.B10, AAV2-r3.45, AAV2-LSS, AAV2PFG, AAV2-PPS, AAV2-TLH or AAV2-GMN capsid protein. In some embodiments, the rAAV particle is an AAV capsid with tissue tropism such as muscle specific, cardiac cells specific or skeletal muscle specific or CNS tissue or cell type specific serotype or AAV capsid particle. [0347] Provided herein is a population of viral particles comprising a plurality of viral particles disclosed herein. Provided herein is a population of retrovirus, lentivirus, adenovirus, AAV or HSV particles. Provided herein is a population of rAAV particles comprising a plurality of rAAV particles disclosed herein. [0348] Provided herein is a cell comprising any of the vectors or viral particles disclosed herein. In some embodiments, the cell is a mammalian cell. In some embodiments, a mammalian cell is a HEK293 cell. In some embodiments, the cell is an insect cell. In some embodiments, the insect cell is a Spodoptera frugiperda cell (for example, the Sf9 or ExpiSf9™ cell lines). The Sf9 insect cell line (Thermo Fisher Scientific, Waltham, MA) is a clonal isolate derived from the parental S. frugiperda cell line IPLB-Sf-21-AE. ExpiSf9™ cells (Thermo Fisher Scientific, Waltham, MA) are a non-engineered derivative of Sf9 insect cells that have been adapted for high-density suspension growth. In some embodiments, the cell is a C8161, CCRF-CEM, MOLT, mIMCD-3, NHDF, HeLa-S3, Huhl, Huh4, Huh7, HUVEC, HASMC, HEKn, HEKa, MiaPaCell, Panc, PC-3, TF1, CTLL-2, CIR, Rat6, CV1, RPTE, A10, T24, J82, A375, ARH-77, Calul, SW480, SW620, SKOV3, SK-UT, CaCo2, P388D1, SEM-K2, WEHI-231, HB56, TIB55, Jurkat, J45.01, LRMB, Bcl-1, BC-3, IC21, DLD2, Raw264.7, NRK, NRK-52E, MRC5, MEF, Hep G2, HeLa B, HeLa T4, COS, COS-1, COS-6, COS-M6A, BS-C-1 monkey kidney epithelial, BALB/3T3 mouse embryo fibroblast, 3T3 Swiss, 3T3-L1, 132-d5 human fetal fibroblasts; 10.1 mouse fibroblasts, 293-T, 3T3, 721, 9L, A2780, A2780ADR, A2780cis, A172, A20, A253, A431, A-549, ALC, B16, B35, BCP-1 cells, BEAS-2B, bEnd.3, BHK-21, BR 293, BxPC3, C3H-10T1/2, C6/36, Cal-27, CHO, CHO-7, CHO—IR, CHO-K1, CHO-K2, CHO-T, CHO Dhfr−/−, COR-L23, COR-L23/CPR, COR-L23/5010, COR-L23/R23, COS-7, COV-434, CML T1, CMT, CT26, D17, DH82, DU145, DuCaP, EL4, EM2, EM3, EMT6/AR1, EMT6/AR10.0, FM3, H1299, H69, HB54, HB55, HCA2, HEK-293, HeLa, Hepalclc7, HL-60, HMEC, HT-29, Jurkat, JY cells, K562 cells, Ku812, KCL22, KG1, KYOl, LNCap, Ma-Mel 1-48, MC-38, MCF-7, MCF-10A, MDA-MB-231, MDA-MB-468, MDA-MB-435, MDCK II, MDCK II, MOR/0.2R, MONO- MAC 6, MTD-1A, MyEnd, NCI-H69/CPR, NCI-H69/LX10, NCI-H69/LX20, NCI- H69/LX4, NIH-3T3, NALM-1, NW-145, OPCN/OPCT cell lines, Peer, PNT-1A/PNT 2, RenCa, RIN-5F, RMA/RMAS, Saos-2 cells, Sf-9, SkBr3, T2, T-47D, T84, THP1 cell line, U373, U87, U937, VCaP, Vero cells, WM39, WT-49, X63, YAC-1, or YAR cell. Pharmaceutical compositions [0349] Provided herein are pharmaceutical compositions comprising any of the vectors, viral particles, nucleic acid molecules, populations of viral particles disclosed herein, and a pharmaceutically acceptable carrier, vehicle or diluent. “Pharmaceutically acceptable” refers to a material that is not toxic or otherwise undesirable, i.e., the material may be administered to a subject without causing any undesirable biological effects. In general, a pharmaceutically acceptable material has one or more benefits that outweigh any undesirable biological effect that the material may have. Undesirable biological effects may include, for example, excessive toxicity, irritation, allergic response, and other problems and complications. [0350] For injection, the carrier will typically be a liquid. For other methods of administration, the carrier may be either solid or liquid. [0351] In some embodiments, a pharmaceutical composition may comprise other medicinal agents, pharmaceutical agents, stabilizing agents, buffers, adjuvants and/or diluents. [0352] In some embodiments, a pharmaceutical composition comprises at least one pharmaceutically acceptable carrier, excipient, and/or vehicle, for example, solvents, buffers, solutions, dispersion media, coatings, antibacterial agents, antifungal agents, isotonic agents, and absorption delaying agents. In some embodiments, the pharmaceutically acceptable carrier, excipient, and/or vehicle comprises saline, buffered saline, dextrose, water, glycerol, sterile isotonic aqueous buffer, or a combination thereof. In some embodiments, the pharmaceutically acceptable carrier, excipient, and/or vehicle comprises phosphate buffered saline, sterile saline, lactose, sucrose, calcium phosphate, dextran, agar, pectin, peanut oil, sesame oil, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol, and the like), or a suitable mixture thereof. In some embodiments, the compositions disclosed herein further comprise emulsifying or wetting agents, or pH buffering agents. Such species may be present in small amounts (e.g., less than 10% by weight of the composition, such as less than 5% by weight of the composition, 2% by weight of the composition, 1% by weight of the composition, or less). [0353] In some embodiments, a pharmaceutical composition further comprises one or more other pharmaceutical ingredients, such as one or more preservatives or chemical stabilizers. Examples of preservatives and chemical stabilizers include, but are not limited to, chlorobutanol, potassium sorbate, sorbic acid, sulfur dioxide, propyl gallate, parabens, ethyl vanillin, glycerin, phenol, parachlorophenol, and albumin. In some embodiments, the compositions disclosed herein further comprise antibacterial agents and/or antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid, and thimerosal; isotonic agents, such as sugars and sodium chloride; and/or agents delaying absorption, such as aluminum monostearate and gelatin. [0354] In some embodiments, a pharmaceutical composition is in a form of an injectable solution or dispersion, such as an aqueous solution or dispersion. In some embodiments, a pharmaceutical composition is a sterile powder for the extemporaneous preparation of sterile injectable solutions or dispersions. Dispersions may be prepared in water, glycerol, liquid polyethylene glycols, oils, or any combination thereof. Delivery vehicles such as liposomes, nanocapsules, microparticles, microspheres, lipid particles, vesicles, and the like, may be used for the introduction of the pharmaceutical compositions provided herein. [0355] In some embodiments, a pharmaceutical composition comprises or consists of a sterile saline (e.g., pharmaceutical grade saline) solution and a vector. In some embodiments, a pharmaceutical composition comprises or consists of a vector and sterile water (e.g., pharmaceutical grade water). In some embodiments, a pharmaceutical composition comprises or consists of a vector and phosphate-buffered saline (PBS) (e.g., pharmaceutical grade PBS). [0356] In some embodiments, a pharmaceutical composition provided herein comprises a vector and one or more excipients. In some embodiments, an excipient is water, a salt solution, an alcohol, a polyethylene glycol, gelatin, lactose, amylase, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose or polyvinylpyrrolidone. [0357] In some embodiments, pharmaceutical compositions provided herein comprise a lipid moiety. For example, a vector may be introduced into preformed liposomes or lipoplexes made of mixtures of cationic lipids and neutral lipids. In some embodiments, vector complexes with mono- or poly-cationic lipids are formed without the presence of a neutral lipid. In some embodiments, a lipid moiety is selected to increase distribution of a pharmaceutical agent to a particular cell or tissue. In some embodiments, a lipid moiety is selected to increase distribution of a pharmaceutical agent to neurons. [0358] In some embodiments, pharmaceutical compositions comprise a delivery system. Examples of delivery systems include, but are not limited to, liposomes and emulsions. Some delivery systems are useful for preparing certain pharmaceutical compositions including those comprising hydrophobic compounds. In some embodiments, organic solvents such as dimethylsulfoxide are used. In some embodiments, pharmaceutical compositions comprise a nanoparticle-based delivery system. In some embodiments, polylactic-co-glycolic acid (PLGA), poly (β-amino esters) (PBAE) and/or polyethylenimine (PEI) are used to formulate nanoparticles. [0359] In some embodiments, pharmaceutical compositions comprise one or more tissue- specific delivery molecules designed to deliver a vector to specific tissues or cell types. For example, in some embodiments, pharmaceutical compositions include liposomes coated with a tissue-specific or a cell-specific antibody. [0360] In some embodiments, pharmaceutical compositions comprise a cosolvent system. Some cosolvent systems comprise, for example, benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. In some embodiments, such cosolvent systems are used for hydrophobic compounds. A non-limiting example of such a cosolvent system is the VPD cosolvent system, which is a solution of absolute ethanol comprising 3% w/v benzyl alcohol, 8% w/v of the nonpolar surfactant Polysorbate 80 and 65% w/v polyethylene glycol 300. The proportions of such cosolvent systems may be varied considerably without significantly altering their solubility and toxicity characteristics. Furthermore, the identity of cosolvent components may be varied: for example, other surfactants may be used instead of Polysorbate 80; the fraction size of polyethylene glycol may be varied; other biocompatible polymers may replace polyethylene glycol, e.g., polyvinyl pyrrolidone; and other sugars or polysaccharides may substitute for dextrose. [0361] Provided herein is a nanoparticle comprising a vector disclosed herein. In some embodiments, a nanoparticle is a lipid nanoparticle. In some embodiments, a nanoparticle is a solid lipid nanoparticle (SLN). [0362] In some embodiments, a pharmaceutical composition comprises a carrier and is formulated in aqueous solution, such as water or physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. In some embodiments, other ingredients are included (e.g., ingredients that aid in solubility or serve as preservatives). In some embodiments, injectable suspensions are prepared using appropriate liquid carriers, suspending agents and the like. In some embodiments, pharmaceutical compositions for injection are prepared in unit dosage form, e.g., in ampoules or in multi- dose containers. Some pharmaceutical compositions for injection are suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Exemplary solvents suitable for use in pharmaceutical compositions for injection include, but are not limited to, lipophilic solvents and fatty oils, such as sesame oil, synthetic fatty acid esters, such as ethyl oleate or triglycerides, and liposomes. [0363] In some embodiments, vectors may be admixed with pharmaceutically acceptable active and/or inert substances for the preparation of pharmaceutical compositions or formulations. Compositions and methods for the formulation of pharmaceutical compositions depend on a number of criteria, including, but not limited to, route of administration, extent of disease, or dose to be administered. [0364] In some embodiments, a pharmaceutical composition is suitable or formulated for systemic administration. In some embodiments, a pharmaceutical composition is suitable or formulated for intravenous administration. [0365] In some embodiments, a pharmaceutical composition is suitable or formulated for intracerebroventricular injection, intrathecal injection, intracarotid artery injection, or intraparenchymal injection. Methods of Producing rAAV Particles [0366] Provided herein are methods of producing rAAV particles by using any of the vectors, AAV expression cassettes, nucleic acid molecules and cells disclosed herein. [0367] Provided herein is a method of producing a rAAV particle, the method comprising: (i) culturing a cell comprising a vector or an AAV expression cassette disclosed herein under conditions allowing for packaging the rAAV particle; and (ii) harvesting the cultured host cell or culture medium for collection of the rAAV particle. [0368] In some embodiments, a method of producing a rAAV particle comprises providing to a cell: (a) a vector (i.e., a nucleic acid template comprising an AAV expression cassette) comprising two AAV ITRs located 5' and 3' to the polynucleotide sequences desired to be packaged into the rAAV particle, and (b) AAV sequences sufficient for replication of the nucleic acid template and encapsidation into AAV protein capsids (e.g., AAV rep sequences and AAV cap sequences encoding the AAV capsid subunits, also referred to as “helper functions”). Typically, the AAV rep and cap sequences will not be flanked by AAV ITRs, to prevent rescue and/or packaging of these sequences. [0369] The vector (nucleic acid template), rep sequences, cap sequences, and any other helper functions required for producing the rAAV particles disclosed herein may be delivered to the packaging host cell using any appropriate genetic element. Further details on methods of preparing rAAV particles are provided in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, NY; Fisher et al, J. Virol., 70:520-532 (1993) and US 5,478,745. [0370] The nucleic acid template and AAV rep and cap sequences are provided under conditions such that virus vector comprising the nucleic acid template packaged within the AAV protein capsid is produced in the cell. The method can further comprise the step of collecting the virus vector from the cell. The virus vector can be collected from the medium and/or by lysing the cells. [0371] The cell can be a cell that is permissive for AAV viral replication. Any suitable cell known in the art may be employed. In some embodiments, the cell is a mammalian cell (e.g., a HEK293 cell). In some embodiments, the cell can be a trans-complementing packaging cell line that provides functions deleted from a replication-defective helper virus, e.g., HEK293 cells or other E1a trans-complementing cells. The helper sequences may be embedded in a chromosome or maintained as a stable extrachromosomal element. [0372] In some embodiments, rAAV particles are produced using the triple transfection method, as described in US 6,001,650. In some embodiments, the rAAVs are produced by transfecting a host cell with an AAV vector (i.e., AAV expression cassette) to be packaged into rAAV particles, an AAV helper function vector, and an accessory function vector. An AAV helper function vector encodes the “AAV helper function” sequences (i.e., rep and cap), which function in trans for productive AAV replication and encapsidation. Non-limiting examples of AAV helper function vectors include pHLP19 and pRep6cap6 vector, described in US 6,001,650 and US 6,156,303, respectively. The accessory function vector encodes nucleotide sequences for non-AAV derived viral and/or cellular functions upon which AAV is dependent for replication (i.e., “accessory functions”). The accessory functions include those functions required for AAV replication, including, without limitation, those moieties involved in activation of AAV gene transcription, stage specific AAV mRNA splicing, AAV DNA replication, synthesis of cap expression products, and AAV capsid assembly. Viral- based accessory functions can be derived from any of the known helper viruses such as adenovirus, herpesvirus (e.g., other than herpes simplex virus type-1) and vaccinia virus. [0373] In some embodiments, rAAVs are produced using recombinant baculovirus vectors. Production of rAAVs using baculovirus vectors is described in, for example, Urabe et al. (2002) Hum Gene Ther 13(16):1935-1943; Smith et al. (2009) Mol Ther 17(11):1888-1896; US 8,945,918; US 9,879,282; and US 2018/0371495. In some embodiments, a baculovirus vector genome is derived from Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), Bombyx mori nuclear polyhedrosis virus (BmNPV), Helicoverpa armigera (HearNPV) or Spodoptera exigua MNPV. Baculovirus vectors are used to produce recombinant AAVs in insect cells (e.g., Spodoptera frugiperda cells). In some embodiments, the Sf9 or ExpiSf9™ Spodoptera frugiperda cell lines are used to produce rAAVs. In some embodiments, methods of the disclosure comprise co-infecting insect cells with populations of recombinant baculoviruses (rBVs) to produce rAAV disclosed herein. At least two populations of rBVs may be used in the methods of the disclosure. Methods for generating recombinant baculovirus are known in the art (see, e.g., the Bac-to-Bac® Baculovirus Expression System (Thermo Fisher Scientific, Waltham, MA)). [0374] In some embodiments, a rAAV particle produced by the methods provided herein comprises an AAV1, AAV2, AAV3 (including types 3A and 3B), AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAVrh32.33, AAVrh.8, AAVrh.10, AAVrh32.33, AAVrh.74, AAVhu.68, avian AAV, bovine AAV, canine AAV, equine AAV, ovine AAV, snake AAV, bearded dragon AAV, AAV2i8, AAV2g9, AAV- LK03, AAV7m8, AAV Anc80, TM-AAV6, AAV-PHP.A, AAV-PHP.B, AAV-PHP.S, AAV- PHPeB, AAV-DJ, AAV-CAP.B10, AAV2-r3.45, AAV2-LSS, AAV2PFG, AAV2-PPS, AAV2-TLH or AAV2-GMN capsid protein. Methods of Using Vectors [0375] Provided herein are methods of modifying the expression of a target gene in a population of cells comprising: contacting a population of cells comprising a target nucleic sequence encoding the target gene with a vector, a viral particle, a population of viral particles, or a pharmaceutical composition disclosed herein, thereby modifying the expression of the target gene. [0376] In some embodiments, the expression of the target gene is increased in the plurality of the modified population of cells in comparison to a population of cells contacted with a vector, a viral particle, a population of viral particles, or a pharmaceutical composition disclosed herein; and a gRNA that does not specifically hybridize to the target nucleic acid sequence, but binds to the Cas-phi polypeptide to form a complex. In some embodiments, the expression of the target gene is increased by at least about 1.10-fold, at least about 1.15-fold, at least about 1.20-fold, at least about 1.25-fold, at least about 1.30-fold, at least about 1.35- fold, at least about 1.40-fold, at least about 1.45-fold, at least about 1.50-fold, at least about 1.55-fold, at least about 1.60-fold, at least about 1.65-fold, at least about 1.70-fold, at least about 1.75-fold, at least about 1.80-fold, at least about 1.85-fold, at least about 1.90-fold, at least about 1.95-fold or at least about 2.0-fold. [0377] Exemplary target genes with increased expression in the plurality of modified the modified population of cells include, but are not limited to those shown in Table 7. [0378] Table 7: Target genes for upregulation. [0379] In some embodiments, the expression of the target gene is decreased in the plurality of the modified population of cells in comparison to a population of cells contacted with a vector, a viral particle, a population of viral particles, or a pharmaceutical composition disclosed herein; and a gRNA that does not specifically hybridize to the target nucleic acid sequence, but binds to the Cas-phi polypeptide to form a complex. In some embodiments, the expression of the target gene is decreased by at least about 1.10-fold, at least about 1.15-fold, at least about 1.20-fold, at least about 1.25-fold, at least about 1.30-fold, at least about 1.35- fold, at least about 1.40-fold, at least about 1.45-fold, at least about 1.50-fold, at least about 1.55-fold, at least about 1.60-fold, at least about 1.65-fold, at least about 1.70-fold, at least about 1.75-fold, at least about 1.80-fold, at least about 1.85-fold, at least about 1.90-fold, at least about 1.95-fold or at least about 2.0-fold. [0380] Exemplary target genes with decreased expression in the plurality of modified the modified population of cells include, but are not limited to those shown in Table 8. [0381] Table 8: Target genes for repression. [0382] Provided herein is a method of reducing or eliminating the expression of a gene product in a subject comprising introducing to a cell of a subject a therapeutically effective amount of a vector, a viral particle, a population of viral particles, or a pharmaceutical composition disclosed herein. [0383] Provided herein is a method for treating or alleviating a symptom of a gene product related disorder in a subject comprising the step of introducing to a cell of the subject a therapeutically effective amount of a vector, a viral particle, a population of viral particles, or a pharmaceutical composition disclosed herein. [0384] In some embodiments, a vector provided herein increases or decreases mRNA expression. Levels of mRNA expression may be measured by a Northern blot, a nuclease protection assay (NPA), in situ hybridization or reverse transcription-polymerase chain reaction (RT-PCR). [0385] In some embodiments, a vector provided herein increases or decreases protein expression. Levels of protein expression may be measured by a Western blot or immunohistochemistry. [0386] In some embodiments, the subject is human. In some embodiments, the subject is less than 2 years old. In some embodiments, the subject is between about 2 years old and about 18 years old. In some embodiments, the subject is older than 18 years. [0387] In some embodiments, the vector, viral particle, population of viral particles or pharmaceutical composition is administered to the subject via intracerebroventricular injection, intrathecal injection, intracarotid artery injection, or intraparenchymal injection. [0388] In some embodiments, the vector, viral particle, population of viral particles or pharmaceutical composition is administered to the subject in a single dose. [0389] Further provided herein is a vector, a viral particle, a population of viral particles or a pharmaceutical composition disclosed herein, for use as a medicament. EXAMPLES [0390] EXAMPLE 1 – Construction of Nuclease Deficient Cas-Phi Polypeptides [0391] Cas-phi targets genomic loci by recognizing a 5’ proto-spacer adjacent motif (PAM) (FIG.1A) sequence and has been shown to be effective at DNA cleaving in human cell lines (Pausch et al., Science 369, 333–337 (2020)). Nuclease deficient Cas-phi (dCas-phi) polypeptides were constructed for the use in the novel gene expression modulation system (GEMS), which was designed to shuttle transcriptional activators or repressors to specific genomic loci and modulate gene expression (FIG.1A). Aspartic acid to alanine mutations of the first RuvC domain (RuvC-I) have been shown to decrease nuclease activity. Additional Cas-phi point mutations and RuvC domain deletions and truncations were added to further eliminate nuclease activity. Such deletions and truncations decrease the size of the nuclease deficient Cas-phi polypeptide, which is advantageous in addressing size limitations of AAV vector delivery in in vivo studies and therapeutic applications. FIG.2A shows a schematic diagram of the nuclease deficient Cas-phi polypeptide mutants that were constructed. FIGS. 2B-2C show amino acid sequence alignments of the nuclease deficient Cas-phi polypeptide mutants with a wildtype Cas-phi-2 polypeptide and wildtype Cas-phi-3 polypeptide, respectively. [0392] Cas-phi-1 mutations [0393] “GEMS 1.1” mutant (2520 bp in length) comprises a D371A mutation in the RuvC-I domain in comparison to a wildtype Cas-Phi-1 polypeptide. [0394] “GEMS 1.2” mutant (2394 bp in length) comprises a D371A mutation in the RuvC-I domain and a RuvC-III domain deletion in comparison to a wildtype Cas-Phi-1 polypeptide. [0395] “GEMS 1.3” mutant (2316 bp in length) comprises a D371A mutation in the RuvC-I domain, a RuvC-III domain deletion and a zinc ribbon deletion in comparison to a wildtype Cas-Phi-1 polypeptide. [0396] Cas-phi-2 mutations [0397] “GEMS 2.1” mutant (2670 bp in length) comprises a D394A in the RuvC-I domain, a E606A mutation in the RuvC-II domain, and a D695A mutation in the RuvC-III domain in comparison to a wildtype Cas-Phi-2 polypeptide. [0398] “GEMS 2.2” mutant (2478 bp in length) comprises a D394A in the RuvC-I domain, a E606A mutation in the RuvC-II domain, and a RuvC-III domain deletion in comparison to a wildtype Cas-Phi-2 polypeptide. [0399] “GEMS 2.3” mutant (2400 bp in length) comprises a D394A in the RuvC-I domain, a E606A mutation in the RuvC-II domain, a RuvC-III domain deletion and a zinc ribbon deletion in comparison to a wildtype Cas-Phi-2 polypeptide. [0400] Cas-phi-3 mutations [0401] “GEMS 3.1” mutant (2697 bp in length) comprises a D413A in the RuvC-I domain, a E618A mutation in the RuvC-II domain, and a D708A mutation in the RuvC-III domain in comparison to a wildtype Cas-Phi-3 polypeptide. [0402] “GEMS 3.2” mutant (2582 bp in length) comprises a D413A in the RuvC-I domain, a E618A mutation in the RuvC-II domain, and a D708A mutation in the RuvC-III domain and a RuvC-III domain deletion in comparison to a wildtype Cas-Phi-3 polypeptide. [0403] “GEMS 3.3” mutant (2225 bp in length) comprises a D413A in the RuvC-I domain, a RuvC-II domain deletion and a RuvC-III domain deletion in comparison to a wildtype Cas- Phi-3 polypeptide. [0404] To test the ability of the mutant Cas-phi variants (Table 3.1) to upregulate gene expression, a VP64 domain was fused to both the N-terminus and the C-terminus of the Cas- phi polypeptide to generate a fusion Cas-phi “GEMS” variant (Table 5.1). N-terminus 3xFLAG domains were additionally fused (not shown) for protein detection via Western blot or immunohistochemistry. [0405] Additional Fusion Cas-Phi GEMS mutants [0406] Next, ten additional nuclease deficient GEMS mutants were constructed by introducing point mutations to only one RuvC domain (FIG.7; Tables 3.2 and 5.2). These mutants were designed by removing the N-terminal VP64, varying the length of the NLS and linker sequence and replacing the C-terminal VP64 with a C-terminal miniVPR (FIG.7). To increase the DNA binding capacity of GEMS mutants, 55 additional GEMS mutant variants with amino acid mutations outside the RuvC domain were constructed (Tables 3.2 and 5.2). [0407] Cloning of Cas-phi mutant constructs [0408] The constructs as shown in FIG.2A and their corresponding gRNAs were synthesized. For in vitro testing, the GEMS constructs were cloned into an AAV vector backbone with two, sequential double digests and Gibson assemblies. First, the AAV vector was digested with XbaI and AfeI to clone in the Cas-phi gRNA scaffold downstream of a U6 promoter using NEBuilder HiFi DNA Assembly (New England Biolabs). Constructs were further digested with EcoRI and NheI to clone in the GEMS sequences (dead-Cas-phi-fusion versions) downstream of a CMV promoter using the In-Fusion HD Cloning kit (Takara). The unique targeting site of 18-23 bases in the sgRNA scaffold was flanked by SapI enzyme site enabling easy swapping of guide RNAs to target unique promoter sequences (FIG.1B). [0409] EXAMPLE 2 – Use of Nuclease Deficient Cas-Phi Polypeptides for Targeted Upregulation of Gene Expression [0410] Each of the “GEMS” constructs were tested in AAVpro HEK293T cells, Kelly neuroblastoma cells or HeLa cells by targeting various genes. Two separate gRNAs each, for Cas-phi-2 and Cas-phi-3 using their respective PAM sequences (Cas-phi-2 PAM: TBN, where ‘B’ is T, C or G and ‘N’ is A, T, C, or G; Cas-phi-3 PAM: VTTY, where ‘V’ is A, G, or C, and ‘Y’ is C or T) (Table 6.1). gRNAs for all three constructs of Cas-phi-2 mutants (GEMS 2.1, GEMS 2.2, GEMS 2.3) and all three constructs of Cas-phi-3 mutants (GEMS 3.1, GEMS 3.2, GEMS 3.3) were constructed. gRNAs for all additional “GEMS” constructs were constructed (Table 6.1). In some instances, the sgRNA scaffold was engineered to remove or include additional bases to improve targeting (Table 6.2) [0411] Transfection [0412] Human embryonic kidney (HEK) 293T cells (AAVpro HEK293T) or Kelly neuroblastoma cells were seeded at a density of 200k/cells per well in a 12-well plate in 1 ml of DMEM media. Cells were transfected with GEMS constructs with either a gene-specific guide or a non-targeting control 24 hours after seeding. Transfection was achieved with 1 or 2 µg of plasmid using X-tremeGENE HP DNA transfection reagent (Roche; for HEK cells) or Lipofectamine LTX (Thermo; for Kelly cells) at a 3:1 ratio (3 µl reagent for every 1 µg plasmid). Plasmids were thoroughly mixed with 100 µl OptiMEM and the transfection reagent and allowed to sit at RT for 20 minutes before adding 100 µl of the mixture dropwise to each well. Cells were harvested 48 hours after transfection. [0413] HeLa cells were seeded at a density of 160k/cells per well in a 12-well plate in 1 ml of EMEM media. Cells were transfected with GEMS constructs with either a gene-specific guide or a non-targeting control 24 hours after seeding. Transfection was achieved with 1ug of plasmid using X-tremeGENE HP DNA transfection reagent at a 2:1 ratio (2 µl reagent for every 1 µg plasmid). Plasmids were thoroughly mixed with 100 µl OptiMEM and the transfection reagent and allowed to sit at RT for 20 minutes before adding 100 µl of the mixture dropwise to each well. RNA was extracted 48 hours after transfection for qPCR analysis. [0414] RNA isolation and quantitative reverse-transcription PCR [0415] RNA was isolated using the Quick-RNA miniprep kit (Zymo) following the manufacturer’s protocol and quantified using Qubit RNA BR reagents (Thermo Fisher). Following RNA isolation, cDNA was prepared using qScript cDNA Synthesis kit (Quantabio) using the manufacturer’s protocol. qPCR was performed with PerfeCTa SYBR Green SuperMix Reagent (Quantabio) and gene-specific primers. Fold change in mRNA expression of the gene of interest was normalized to ACTB or GAPDH expression using the ΔΔCT method. [0416] Luciferase reporter assay [0417] Human embryonic kidney (HEK) 293T cells (AAVpro HEK293T) were seeded at a density of 20k/cells per well in a 96-well plate in 75 µl of DMEM media. Cells were triple transfected with GEMS constructs, the Firefly luciferase reporter vector (Promega; pGL4.23c) with the SYNGAP1 promoter cloned upstream of the luciferase gene and a promoterless Renilla vector (Promega; pGL4.70) at a 5:10:1 plasmid ratio (100 ng/well total DNA) using XtremeGENE HP DNA transfection reagent at a 2:1 ratio (2 ul reagent for every 1 µg plasmid). Each transfection was performed in quadruplicate. Luciferase expression was measured 48-hours post transfection by following the manufacturer’s protocol for Promega’s Dual-Glo Luciferase Assay System (E2940). Luminance was read by a plate reader (Agilent Cytation 5) and fold change was calculated by dividing the average signal from the targeting guide by the signal from a non-targeting control. [0418] Each of the fusion Cas-phi “GEMS” constructs were tested in AAVpro HEK293T cells by targeting STXBP1 (NCBI Gene id: 6812) gene. Fold-change of target gene expression over non-targeting guides was measured (FIGS.3A-3B). GEMS 2.3 and GEMS 3.3 constructs consistently resulted in upregulation of STXBP1 over non targeting guide controls (Table 9). [0419] Table 9: Fold change per STXBP1-targeting replicate [0420] The fusion Cas-phi GEMS variants can upregulate SYNGAP1 (Gene id: 8831) in a neuroblastoma cell line (FIGS.4A-4B; Table 10), demonstrating the ability of the variants to upregulate gene expression across different cell types. [0421] A subset of fusion Cas-phi GEMS variants from Table 5.2 were constructed and tested using a luciferase reporter assay. The promoter sequence of human SYNGAP1 (Gene id: 8831) was cloned upstream of the luciferase coding sequence in a reporter vector and was co-transfected with a GEMS mutants expression vector in HEK293T cells. Binding of GEMS mutants at the promoter results in an increase in luciferase expression, which is measured as a relative increase in luminescence compared to a non-targeting control. [0422] It was observed that multiple guide pairs (SYNGAPg3, SYNGAPg4, SYNGAPg5, SYNGAPg6, SYNGAPg7, SYNGAPg8, SYNGAPg9 of Table 6.1) used in combination with a mature scaffold sequence (Table 6.2) and with GEMS 2.1 and 3.1, respectively, were effective at increasing gene expression directed from the SYNGAP1 promoter (relative to a non-targeting control) (FIG.6). Further testing of SYNGAPg7 guide RNA with additional fusion Cas-phi GEMS variants containing only a C-terminal VP64 or miniVPR (Table 5.2) showed upregulation at the endogenous locus in neuroblastoma cells and HEK293T cells or Kelly neuroblastoma cells(FIGS.8-10). [0423] Table 10: Fold change per SYNGAP-targeting replicate. [0424] The fusion Cas-phi GEMS variants can upregulate ASCL1 (Gene id: 429) in AAVpro HEK293T cells (FIG.5A; Table 11), further demonstrating the ability of the GEMS variants to upgregulate different genes. This data also suggests that 20 bp gRNAs are more effective at than 23 bp gRNAs for GEMS (FIG.5B; Table 11). [0425] Table 11: Fold change per ASCL1-targeting replicate. [0426] The fusion Cas-phi GEMS variants can upregulate IL1RN (Gene id: 3557) in HeLa cells (FIG.11A-11B; Table 12), further demonstrating the ability of GEMS variants to upgregulate different genes. Finally, a subset of GEMS variants with a C-terminal miniVPR were demonstrated to upregulate IL1RN (Gene id: 3557) in HeLa cells (FIG.11A-11B). [0427] Table 12: Fold change per IL1RN-targeting replicate. INCORPORATION BY REFERENCE [0428] Throughout this application various publications, patents, and/or patent applications are referenced. The disclosures of the publications, patents and/or patent applications are hereby incorporated by reference in their entireties into this application in order to more fully describe the state of the art to which this disclosure pertains. EQUIVALENTS [0429] The details of one or more embodiments of the disclosure are set forth in the accompanying description above. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms include plural referents unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited in this specification are incorporated by reference. [0430] The foregoing description has been presented only for the purposes of illustration and is not intended to limit the disclosure to the precise form disclosed, but by the claims appended hereto. EMBODIMENTS [0431] Additional embodiments of the disclosure include the following: [0432] Embodiment 1. A composition comprising: a) a Cas-phi polypeptide or a polynucleotide sequence encoding the Cas-phi polypeptide, wherein the Cas-phi polypeptide comprises at least one RuvC domain and wherein the at least one RuvC domain is nuclease inactive and the RuvC domain comprises at least one mutation relative to a wildtype RuvC domain; and b) a polynucleotide sequence encoding a guide RNA (gRNA) that can specifically hybridize to a target nucleic sequence and to the Cas phi polypeptide to form a complex. [0433] Embodiment 2. The composition of embodiment 1, wherein the Cas-phi polypeptide is a Cas-phi-1, a Cas-phi-2 or a Cas-phi-3 polypeptide. [0434] Embodiment 3. The composition of embodiment 2, wherein the Cas-phi polypeptide is a Cas-phi-2, and wherein the at least one mutation is i) D394A; ii) D394A and E606A; iii) D394A and D695A; or iv) D394A, E606A and D695A, numbered in accordance to SEQ ID NO: 4. [0435] Embodiment 4. The composition of embodiment 2, wherein the Cas-phi polypeptide is a Cas-phi-3, and wherein the at least one mutation is i) D413A; ii) D413A and E618A; iii) D413A and D708A; or iv) D413A, E618A and D708A, numbered in accordance to SEQ ID NO: 6. [0436] Embodiment 5. The composition of embodiment 2, wherein the Cas-phi polypeptide is a Cas-phi-1, and wherein the at least one mutation is D371A, numbered in accordance to SEQ ID NO: 2. [0437] Embodiment 6. The composition of any one of embodiments 1-5, wherein the Cas-phi polypeptide further comprises a deletion of a RuvC domain in comparison to a wildtype Cas-phi polypeptide, wherein the deletion of the RuvC domain is a RuvC-II domain deletion and/or a RuvC-III domain deletion. [0438] Embodiment 7. The composition of any one to embodiments 1-2, wherein the Cas-phi polypeptide further comprises a deletion of a zinc ribbon domain in comparison to a wildtype Cas-phi polypeptide. [0439] Embodiment 8. The composition of any one of embodiments 1-7, wherein the Cas-phi polypeptide comprises the amino acid sequence of SEQ ID NO: 28, 30, 32, 34, 36, 38, 40, 42 or 44. [0440] Embodiment 9. The composition of any one of embodiments 1-7, wherein the Cas-phi polypeptide comprises an amino acid sequence at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or about 99% identical to the amino acid sequence of SEQ ID NO: 28, 30, 32, 34, 36, 38, 40, 42 or 44. [0441] Embodiment 10. The composition of any one of embodiments 1-9, wherein the Cas-phi polypeptide or the polynucleotide sequence encoding the Cas-phi polypeptide is fused to at least one effector domain or a polynucleotide sequence encoding the effector domain. [0442] Embodiment 11. The composition of embodiment 10, wherein the at least one effector domain is fused to i) the N-terminus of the Cas-phi polypeptide, ii) the C-terminus of the Cas-phi polypeptide, or iii) both the N-terminus and the C-terminus of the Cas-phi polypeptide. [0443] Embodiment 12. The composition of embodiment 11, wherein the at least one effector domain fused to the N-terminus of the Cas-phi polypeptide and the C-terminus of the Cas-phi polypeptide are different. [0444] Embodiment 13. The composition of embodiment 11, wherein the at least one effector domain fused to the N-terminus of the Cas-phi polypeptide and the C-terminus of the Cas-phi polypeptide are the same. [0445] Embodiment 14. The composition of any one of embodiments 10-13, wherein the at least one effector domain comprises an effector domain derived from a p65 NF-Κβ transactivating subunit (p65), VP160, SET7, RTA, histone acetyltransferase p300, VPR, MyoDl, TET1 hydroxylase catalytic domain, LSDI, Cmi, AD2, CR3, GATA4, p53, MEF2C, TAX, PPARy, SET9, KRAB, DNMT3A, DNMT1, KRAB-MeCP2, SIN3A, Mxi1, SID4x or Dnmt3a3L or a combination thereof. [0446] Embodiment 15. The composition of any one of embodiments 1-14, wherein the target nucleic acid sequence of b) is a regulatory region of a gene. [0447] Embodiment 16. The composition of embodiment 15, wherein the regulatory region is a promoter or an enhancer. [0448] Embodiment 17. The composition of any one of embodiments 1-16, wherein the target nucleic sequence of b) encodes a gene product, and wherein the gene product is A4GALT, AAGAB, ABCD1, ACSL4, ACTC1, ACVRL1, ADNP, AFF2, AHDC1, AKT3, ALX4, ANK2, ANKRD11, ANOS1, AP1S2, APC, AR, ARCN1, ARHGEF9, ARID1A, ARID1B, ARID2, ARSE, ARX, ASH1L, ASXL1, ASXL3, ATP7A, ATP8A2, ATRX, AUTS2, AVPR2, AXIN2, BAG3, BCL11A, BCLAF1, BCOR, BMP4, BMPR1A, BMPR2, BRAF, BRCA1, BRCA2, BRIP1, BRWD3, BTK, CACNA1A, CACNA1C, CAMK2A, CAMK2B, CAMTA1, CASK, CASZ1, CCNQ, CDC42BPB, CDH1, CDKL5, CDKN1C, CFC1, CHAMP1, CHD2, CHD7, CHD8, CHM, CHRDL1, CHRM3, CIC, CLCN4, CLCN5, CNKSR2, CNTN4, CNTN6, CNTNAP2, COL11A1, COL1A1, COL2A1, COL3A1, COL4A5, COL5A1, CREBBP, CRYBB2, CSMD1, CTCF, CTNNB1, CTNND2, CUL3, CUL4B, CYBB, DCHS1, DCX, DDX3X, DICER1, DIP2A, DKC1, DLG2, DLG3, DMD, DMRT1, DNMT3A, DPP6, DSC2, DSCAM, DSG2, DSP, DYRK1A, EBP, EDA, EDNRB, EFNB1, EFTUD2, EHMT1, ELAVL2, ELN, EMX2, ENG, EP300, ERF, ERMARD, EXT1, EXT2, EYA1, EYA4, F8, F9, FANCB, FAS, FBN1, FGD1, FGF10, FGFR1, FLCN, FLG, FLNA, FMR1, FOXC1, FOXC2, FOXF1, FOXG1, FOXL2, FOXP1, FOXP2, FRMD7, FTSJ1, FZD4, GABRA1, GABRG2, GATA2, GATA3, GATA4, GATA6, GATAD2B, GCH1, GDF5, GDI1, GIGYF2, GJA5, GJA8, GK, GLA, GLI2, GLI3, GLMN, GNAS, GNB1, GPC3, GPHN, GRIA3, GRIN2A, GRIN2B, HCCS, HDAC4, HDAC8, HIST1H1E, HIVEP2, HIVEP3, HMGA2, HNF1B, HNRNPK, HNRNPU, HOXD13, HPRT1, IDS, IGF1R, IKBKG, IL1RAPL1, IQSEC2, IRF6, ITSN1, JAG1, KANSL1, KAT6A, KAT6B, KATNAL2, KCNH2, KCNQ1, KCNQ2, KDM5B, KDM5C, KDM6A, KDM6B, KIF11, KMT2A, KMT2B, KMT2C, KMT2D, L1CAM, LAMP2, LDLR, LEMD3, LHX4, LMNA, LMTK3, LMX1B, LRP5, MAGEL2, MAGT1, MAOA, MAP2K2, MBD5, MECP2, MED13L, MEF2C, MEIS2, MEN1, MID1, MITF, MLH1, MNX1, MSH2, MSH6, MSX2, MTAP, MTM1, MYBPC3, MYCN, MYH10, MYLK, MYT1L, NAA15, NBEA, NCKAP1, NDP, NEDD9, NEXMIF, NF1, NF2, NFIA, NHS, NIPBL, NKX2-5, NODAL, NR0B1, NR3C2, NR5A1, NRXN1, NSD1, NSDHL, NXF5, NYX, OCRL, OFD1, OPHN1, OTC, OTX2, PAFAH1B1, PAK2, PAK3, PAX2, PAX3, PAX6, PAX8, PAX9, PCDH19, PDHA1, PGK1, PHEX, PHF2, PHF21A, PHF3, PHF6, PHF8, PHIP, PIGA, PITX2, PKD1, PKD2, PKP2, PLP1, PMP22, PMS2, POGZ, POLR1D, PORCN, PQBP1, PRPS1, PTCH1, PTCHD1, PTEN, PTHLH, PTPN11, PURA, RAB39B, RAI1, RALGAPB, RASA1, RB1, RB1CC1, RET, RIMS1, RNF135, RP2, RPH3A, RPL15, RPS17, RPS19, RPS24, RPS26, RPS6KA3, RS1, RUNX1, SALL1, SALL4, SATB2, SCN1A, SCN2A, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SEMA3A, SETBP1, SETD1A, SETD2, SETD5, SF3B4, SGCE, SH2B1, SH2D1A, SHANK1, SHANK2, SHANK3, SHH, SHOX, SIM1, SIX3, SLC16A12, SLC16A2, SLC17A8, SLC2A1, SLC35A2, SLC4A10, SLC6A1, SLC6A8, SLC9A6, SMAD3, SMAD4, SMARCA4, SMARCB1, SMC1A, SMS, SNURF, SON, SOX10, SOX11, SOX2, SOX5, SOX9, SPAST, SPEN, SPINK1, SPRED1, SRCAP, SRY, STK11, STS, STXBP1, SYN1, SYNGAP1, SYP, TAB2, TAF13, TBL1XR1, TBR1, TBX1, TBX2, TBX20, TBX22, TBX3, TBX4, TBX5, TCF12, TCF20, TCF4, TCF7L2, TCOF1, TDGF1, TERT, TFAP2B, TGFBR1, TGFBR2, TGIF1, TIMM8A, TMLHE, TNNI3, TNRC6B, TP53, TP63, TRAPPC2, TRIO, TRIP12, TRPS1, TRRAP, TSC1, TSC2, TSPAN7, TWIST1, UBE2A, UBE3A, UBN2, UPF3B, USP9X, VEGFA, VHL, WAC, WDFY3, WDR45, WT1, XIAP, YAP1, YTHDC1, ZBTB18, ZC4H2, ZDHHC9, ZEB2, ZFPM2, ZIC1, ZIC2, ZIC3, ZIC4, ZMYND11, ZNF41, ZNF462, ZNF674, ZNF711 or ZWILCH. [0449] Embodiment 18. The composition of any one of embodiments 1-16, wherein the target nucleic sequence of b) encodes a gene product, and wherein the gene product is MT- TL1, KCNQ2, DEAF1, SSBP1, KCNQ1, HNF1B, KAT6B, CDK8, MN1, COL4A1, CDKL5, VAPB, NALCN, TTR, RAC2, GJB2, MYO3A, MEIS2, BRCA2, NARS1, AIRE, GABRG3, RAD51, GATA6, PDX1, ETV6, BCL11B, CHEK2, WARS1, KAT6B, KCNQ1, PRNP, MAT1A, HCN4, DSG2, MAFB, ZSWIM6, WT1, NIPBL, COL9A3, MYH7, SMAD4, IL6ST, CAPN3, KCNK18, DDX3X, SCAMP5, APC, CEBPA, RBM20, PMS2, BEST1, HCN1, PKD1, MSH2, RAD50, EYA1, KCNQ2, PRKCE, SYT1, GNAS, GSDME, LMX1B, MECP2, LZTR1, KLHL7, SLC6A1, SUFU, CREBBP, KCNQ3, PPP2R1A, TOR1A, TGFBR1, COL5A1, SNAP25, GABBR2, SHANK3, PEX6, PPP2R5D, ATP1A3, KDM6A, TPM2, HNF4A, POLG, TUBB4A, PYGM, CPT2, BRCA1, LDLR, KCND2, NFKBIA, RPE65, PRPH2, BARD1, SDHD, PHKG2, MYL2, KCNK9, SPTB, TGFBR2, SSBP1, ATL1, CSF1R, SLC25A4, KAT6A, SATB2, POU3F3, SHOX, ENG, NOVA2, OTX2, PACS1, FBXO38, ALDH18A1, KCNC1, AARS1, CDKN2A, BBS7, PAX2, GNAO1, COL12A1, BLM, POGZ, TRPV4, FLG, FGFR1, KIF2A, ERF, EBF3, BRAF, RET, PDHA1, SPTAN1, PALB2, FASLG, TBC1D24, NOTCH3, FBN1, COL2A1, RRM2B, GLRA1, BMPR1A, MLH1, TCF3, THRB, CACNA1A, PKD2, ACVRL1, KIF5A, GLI3, KCNH1, GRIN2D, SHOC2, TP53, NTRK2, SPTLC1, GUCY2D, TPM1, CDH1, SPAST, NSD1, WFS1, PDE4D, PBX1, CBL, PMP22, DIAPH1, DMPK, GCK, KCNH2, TPP1, FANCC, FAS, BBS2, ABCC8, F11, KCNC3, MFN2, MPZ, CLCN1, PPP2CA, KCNJ2, SDHB, SPTBN2, CAPZA2, KLF1, NFIX, IFNGR1, COL1A2, MAPK8IP3, SCN5A, SRCAP, TP63, KCNA2, CDK13, CASQ2, TNNT1, DNM1L, SALL1, RHOA, KIF1A, RYR1, STAT3, HNF1A, COL7A1, PIK3CA, MYBPC3, CTCF, PTPN11, ATM, DEAF1, KCNT2, HMBS, ITPR1, TM4SF20, ASXL2, COL4A4, ADAR, DES, SCN2A, SLC4A1, HNF1B, BRIP1, FOXP1, KCNA1, MCCC1, BMPR2, MSH6, KRT9, MUTYH, RAF1, FH, ATAD3A, CASR, LMNA, REEP1, VHL, GATA2, DHDDS, ARID1A, NF1, RAD51C, KCNQ4, TNNT2, CXCR4, RYR2, ALPL, TPM3, SMN1, SERPINF1, PCGF2, SURF1, ATAD1, PTEN, TNFRSF11A, JAG1, ATP7B, CACNA1C, SLC16A2, SALL4, GJB6, MORC2, STING1, CHRNA4, TECPR2, GNA11, HEXB, HOGA1, DONSON, RRAS2, SLC6A8, SH3BP2, GNAQ, FLNA, PPP1CB, BICD2, ARID1B, PRKG1, TYR, ANKRD26, PHOX2B, EPAS1, PIK3R1, AFF4, MTOR, SAMD9L, ALK, SAMD9, PAH, PIEZO1, SOS2, STING1, HGSNAT, ABL1, AKT1, PDGFRB, GAMT, SLC35A3, CAMK2G, ATAD1, SURF1, IGHMBP2, GARS1, GLUD1, FGFR2, SMN1, FGFR3, MEFV, IDH2, KCNT1, VWF, GRIK2, SLC12A3, MAP2K1, KIF21A, PTEN, COG4, STAT1, CARD11, PMP2, SERPINF1, SPOP, STIM1, LAMB3, NLRC4, ITGB3, PNPO, CLCN2, SCN11A, NLRP3, IDH1, RIT1, TRIO, ADCY5, DNM2, SCN1B, SLC26A2, SCN8A, ALG1, KCNJ11, CHRNA1, MAP2K2, IFIH1, ACAD9, PKP2, CACNA1C, ORC1, UBTF, C3, KRAS, FANCA, FGF12, TIA1, HOXD13, CHRNB2, PSEN2, ACADM, MPL, SCN1A, GLMN, NRAS, RARB, PRKAR1A, SOS1, PCGF2, CACNA1E, PIK3CD or F5. [0450] Embodiment 19. A vector comprising: the nucleic acid sequence encoding the Cas-phi polypeptide of (a) and the polynucleotide sequence encoding the gRNA of (b) of any one of embodiments 1-18. [0451] Embodiment 20. The vector of embodiment 19, wherein the gRNA is operatively linked to a promoter recognized by RNA polymerase III. [0452] Embodiment 21. The vector of embodiment 20, wherein the gRNA is operatively linked to a human U6 promoter. [0453] Embodiment 22. The vector of any one of embodiments 19-21, wherein the vector is a viral vector. [0454] Embodiment 23. The vector of embodiment 22, wherein the viral vector is an adeno-associated virus (AAV) vector. [0455] Embodiment 24. The vector of any one of embodiments 1-21, wherein the vector is suitable for delivery via a non-viral delivery system. [0456] Embodiment 25. The vector of embodiment 24, wherein the non-viral delivery system is a lipid nanoparticle or an exosome. [0457] Embodiment 26. A viral particle comprising the vector of any one of embodiments 19-23. [0458] Embodiment 27. The viral particle of embodiment 26, wherein the viral particle is a recombinant AAV (rAAV) particle. [0459] Embodiment 28. The viral particle of embodiment 27, wherein the rAAV particle is an AAV9, AAV-PHP.eB, AAV-DJ, AAV2, MyoAAV, AAV1, AAV5, AAV6 or AAV8. [0460] Embodiment 29. A population of viral particles comprising a plurality of viral particles of any one of embodiments 26-28. [0461] Embodiment 30. A pharmaceutical composition comprising the vector of any one of embodiments 19-25, the viral particle of any one of embodiments 26-28 or the population of embodiment 29, and a pharmaceutically acceptable carrier, vehicle or diluent. [0462] Embodiment 31. A cell comprising the vector of any one of embodiments 19-25 or the viral particle of any one of embodiments 26-28. [0463] Embodiment 32. The cell of embodiment 31, wherein the cell is a mammalian cell or an insect cell. [0464] Embodiment 33. A method of modifying the expression of a target gene in a population of cells comprising: contacting a population of cells comprising a target nucleic sequence encoding the target gene with the vector of any one of embodiments 19-25, the viral particle of any one of embodiments 26-28, the population of embodiment 29 or the pharmaceutical composition of embodiment 30, thereby modifying the expression of the target gene. [0465] Embodiment 34. The method of embodiment 33, wherein the expression of the target gene is increased in the plurality of the modified population of cells in comparison to a population of cells contacted with the vector of any one of embodiments 19-25, the viral particle of any one of embodiments 26-28, the population of embodiment 29 or the pharmaceutical composition of embodiment 30; and a gRNA that does not specifically hybridize to the target nucleic acid sequence, but binds to the Cas-phi polypeptide to form a complex. [0466] Embodiment 35. The method of embodiment 34, wherein the expression of the target gene is increased by at least about 1.10-fold, at least about 1.15-fold, at least about 1.20-fold, at least about 1.25-fold, at least about 1.30-fold, at least about 1.35-fold, at least about 1.40-fold, at least about 1.45-fold, at least about 1.50-fold, at least about 1.55-fold, at least about 1.60-fold, at least about 1.65-fold, at least about 1.70-fold, at least about 1.75- fold, at least about 1.80-fold, at least about 1.85-fold, at least about 1.90-fold, at least about 1.95-fold or at least about 2.0-fold. [0467] Embodiment 36. The method of any one of embodiments 33-35, wherein the target gene is A4GALT, AAGAB, ABCD1, ACSL4, ACTC1, ACVRL1, ADNP, AFF2, AHDC1, AKT3, ALX4, ANK2, ANKRD11, ANOS1, AP1S2, APC, AR, ARCN1, ARHGEF9, ARID1A, ARID1B, ARID2, ARSE, ARX, ASH1L, ASXL1, ASXL3, ATP7A, ATP8A2, ATRX, AUTS2, AVPR2, AXIN2, BAG3, BCL11A, BCLAF1, BCOR, BMP4, BMPR1A, BMPR2, BRAF, BRCA1, BRCA2, BRIP1, BRWD3, BTK, CACNA1A, CACNA1C, CAMK2A, CAMK2B, CAMTA1, CASK, CASZ1, CCNQ, CDC42BPB, CDH1, CDKL5, CDKN1C, CFC1, CHAMP1, CHD2, CHD7, CHD8, CHM, CHRDL1, CHRM3, CIC, CLCN4, CLCN5, CNKSR2, CNTN4, CNTN6, CNTNAP2, COL11A1, COL1A1, COL2A1, COL3A1, COL4A5, COL5A1, CREBBP, CRYBB2, CSMD1, CTCF, CTNNB1, CTNND2, CUL3, CUL4B, CYBB, DCHS1, DCX, DDX3X, DICER1, DIP2A, DKC1, DLG2, DLG3, DMD, DMRT1, DNMT3A, DPP6, DSC2, DSCAM, DSG2, DSP, DYRK1A, EBP, EDA, EDNRB, EFNB1, EFTUD2, EHMT1, ELAVL2, ELN, EMX2, ENG, EP300, ERF, ERMARD, EXT1, EXT2, EYA1, EYA4, F8, F9, FANCB, FAS, FBN1, FGD1, FGF10, FGFR1, FLCN, FLG, FLNA, FMR1, FOXC1, FOXC2, FOXF1, FOXG1, FOXL2, FOXP1, FOXP2, FRMD7, FTSJ1, FZD4, GABRA1, GABRG2, GATA2, GATA3, GATA4, GATA6, GATAD2B, GCH1, GDF5, GDI1, GIGYF2, GJA5, GJA8, GK, GLA, GLI2, GLI3, GLMN, GNAS, GNB1, GPC3, GPHN, GRIA3, GRIN2A, GRIN2B, HCCS, HDAC4, HDAC8, HIST1H1E, HIVEP2, HIVEP3, HMGA2, HNF1B, HNRNPK, HNRNPU, HOXD13, HPRT1, IDS, IGF1R, IKBKG, IL1RAPL1, IQSEC2, IRF6, ITSN1, JAG1, KANSL1, KAT6A, KAT6B, KATNAL2, KCNH2, KCNQ1, KCNQ2, KDM5B, KDM5C, KDM6A, KDM6B, KIF11, KMT2A, KMT2B, KMT2C, KMT2D, L1CAM, LAMP2, LDLR, LEMD3, LHX4, LMNA, LMTK3, LMX1B, LRP5, MAGEL2, MAGT1, MAOA, MAP2K2, MBD5, MECP2, MED13L, MEF2C, MEIS2, MEN1, MID1, MITF, MLH1, MNX1, MSH2, MSH6, MSX2, MTAP, MTM1, MYBPC3, MYCN, MYH10, MYLK, MYT1L, NAA15, NBEA, NCKAP1, NDP, NEDD9, NEXMIF, NF1, NF2, NFIA, NHS, NIPBL, NKX2-5, NODAL, NR0B1, NR3C2, NR5A1, NRXN1, NSD1, NSDHL, NXF5, NYX, OCRL, OFD1, OPHN1, OTC, OTX2, PAFAH1B1, PAK2, PAK3, PAX2, PAX3, PAX6, PAX8, PAX9, PCDH19, PDHA1, PGK1, PHEX, PHF2, PHF21A, PHF3, PHF6, PHF8, PHIP, PIGA, PITX2, PKD1, PKD2, PKP2, PLP1, PMP22, PMS2, POGZ, POLR1D, PORCN, PQBP1, PRPS1, PTCH1, PTCHD1, PTEN, PTHLH, PTPN11, PURA, RAB39B, RAI1, RALGAPB, RASA1, RB1, RB1CC1, RET, RIMS1, RNF135, RP2, RPH3A, RPL15, RPS17, RPS19, RPS24, RPS26, RPS6KA3, RS1, RUNX1, SALL1, SALL4, SATB2, SCN1A, SCN2A, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SEMA3A, SETBP1, SETD1A, SETD2, SETD5, SF3B4, SGCE, SH2B1, SH2D1A, SHANK1, SHANK2, SHANK3, SHH, SHOX, SIM1, SIX3, SLC16A12, SLC16A2, SLC17A8, SLC2A1, SLC35A2, SLC4A10, SLC6A1, SLC6A8, SLC9A6, SMAD3, SMAD4, SMARCA4, SMARCB1, SMC1A, SMS, SNURF, SON, SOX10, SOX11, SOX2, SOX5, SOX9, SPAST, SPEN, SPINK1, SPRED1, SRCAP, SRY, STK11, STS, STXBP1, SYN1, SYNGAP1, SYP, TAB2, TAF13, TBL1XR1, TBR1, TBX1, TBX2, TBX20, TBX22, TBX3, TBX4, TBX5, TCF12, TCF20, TCF4, TCF7L2, TCOF1, TDGF1, TERT, TFAP2B, TGFBR1, TGFBR2, TGIF1, TIMM8A, TMLHE, TNNI3, TNRC6B, TP53, TP63, TRAPPC2, TRIO, TRIP12, TRPS1, TRRAP, TSC1, TSC2, TSPAN7, TWIST1, UBE2A, UBE3A, UBN2, UPF3B, USP9X, VEGFA, VHL, WAC, WDFY3, WDR45, WT1, XIAP, YAP1, YTHDC1, ZBTB18, ZC4H2, ZDHHC9, ZEB2, ZFPM2, ZIC1, ZIC2, ZIC3, ZIC4, ZMYND11, ZNF41, ZNF462, ZNF674, ZNF711 or ZWILCH. [0468] Embodiment 37. The method of embodiment 33, wherein the expression of the target gene is decreased in the plurality of the modified population of cells in comparison to a population of cells contacted with the vector of any one of embodiments 19-25, the viral particle of any one of embodiments 26-28, the population of embodiment 29 or the pharmaceutical composition of embodiment 30; and a gRNA that does not specifically hybridize to the target nucleic acid sequence, but binds to the Cas-phi polypeptide to form a complex. [0469] Embodiment 38. The method of embodiment 37, wherein the expression of the target gene is decreased by at least about 1.10-fold, at least about 1.15-fold, at least about 1.20-fold, at least about 1.25-fold, at least about 1.30-fold, at least about 1.35-fold, at least about 1.40-fold, at least about 1.45-fold, at least about 1.50-fold, at least about 1.55-fold, at least about 1.60-fold, at least about 1.65-fold, at least about 1.70-fold, at least about 1.75- fold, at least about 1.80-fold, at least about 1.85-fold, at least about 1.90-fold, at least about 1.95-fold or at least about 2.0-fold. [0470] Embodiment 39. The method of any one of embodiments 33, 37 or 38, wherein the target gene is MT-TL1, KCNQ2, DEAF1, SSBP1, KCNQ1, HNF1B, KAT6B, CDK8, MN1, COL4A1, CDKL5, VAPB, NALCN, TTR, RAC2, GJB2, MYO3A, MEIS2, BRCA2, NARS1, AIRE, GABRG3, RAD51, GATA6, PDX1, ETV6, BCL11B, CHEK2, WARS1, KAT6B, KCNQ1, PRNP, MAT1A, HCN4, DSG2, MAFB, ZSWIM6, WT1, NIPBL, COL9A3, MYH7, SMAD4, IL6ST, CAPN3, KCNK18, DDX3X, SCAMP5, APC, CEBPA, RBM20, PMS2, BEST1, HCN1, PKD1, MSH2, RAD50, EYA1, KCNQ2, PRKCE, SYT1, GNAS, GSDME, LMX1B, MECP2, LZTR1, KLHL7, SLC6A1, SUFU, CREBBP, KCNQ3, PPP2R1A, TOR1A, TGFBR1, COL5A1, SNAP25, GABBR2, SHANK3, PEX6, PPP2R5D, ATP1A3, KDM6A, TPM2, HNF4A, POLG, TUBB4A, PYGM, CPT2, BRCA1, LDLR, KCND2, NFKBIA, RPE65, PRPH2, BARD1, SDHD, PHKG2, MYL2, KCNK9, SPTB, TGFBR2, SSBP1, ATL1, CSF1R, SLC25A4, KAT6A, SATB2, POU3F3, SHOX, ENG, NOVA2, OTX2, PACS1, FBXO38, ALDH18A1, KCNC1, AARS1, CDKN2A, BBS7, PAX2, GNAO1, COL12A1, BLM, POGZ, TRPV4, FLG, FGFR1, KIF2A, ERF, EBF3, BRAF, RET, PDHA1, SPTAN1, PALB2, FASLG, TBC1D24, NOTCH3, FBN1, COL2A1, RRM2B, GLRA1, BMPR1A, MLH1, TCF3, THRB, CACNA1A, PKD2, ACVRL1, KIF5A, GLI3, KCNH1, GRIN2D, SHOC2, TP53, NTRK2, SPTLC1, GUCY2D, TPM1, CDH1, SPAST, NSD1, WFS1, PDE4D, PBX1, CBL, PMP22, DIAPH1, DMPK, GCK, KCNH2, TPP1, FANCC, FAS, BBS2, ABCC8, F11, KCNC3, MFN2, MPZ, CLCN1, PPP2CA, KCNJ2, SDHB, SPTBN2, CAPZA2, KLF1, NFIX, IFNGR1, COL1A2, MAPK8IP3, SCN5A, SRCAP, TP63, KCNA2, CDK13, CASQ2, TNNT1, DNM1L, SALL1, RHOA, KIF1A, RYR1, STAT3, HNF1A, COL7A1, PIK3CA, MYBPC3, CTCF, PTPN11, ATM, DEAF1, KCNT2, HMBS, ITPR1, TM4SF20, ASXL2, COL4A4, ADAR, DES, SCN2A, SLC4A1, HNF1B, BRIP1, FOXP1, KCNA1, MCCC1, BMPR2, MSH6, KRT9, MUTYH, RAF1, FH, ATAD3A, CASR, LMNA, REEP1, VHL, GATA2, DHDDS, ARID1A, NF1, RAD51C, KCNQ4, TNNT2, CXCR4, RYR2, ALPL, TPM3, SMN1, SERPINF1, PCGF2, SURF1, ATAD1, PTEN, TNFRSF11A, JAG1, ATP7B, CACNA1C, SLC16A2, SALL4, GJB6, MORC2, STING1, CHRNA4, TECPR2, GNA11, HEXB, HOGA1, DONSON, RRAS2, SLC6A8, SH3BP2, GNAQ, FLNA, PPP1CB, BICD2, ARID1B, PRKG1, TYR, ANKRD26, PHOX2B, EPAS1, PIK3R1, AFF4, MTOR, SAMD9L, ALK, SAMD9, PAH, PIEZO1, SOS2, STING1, HGSNAT, ABL1, AKT1, PDGFRB, GAMT, SLC35A3, CAMK2G, ATAD1, SURF1, IGHMBP2, GARS1, GLUD1, FGFR2, SMN1, FGFR3, MEFV, IDH2, KCNT1, VWF, GRIK2, SLC12A3, MAP2K1, KIF21A, PTEN, COG4, STAT1, CARD11, PMP2, SERPINF1, SPOP, STIM1, LAMB3, NLRC4, ITGB3, PNPO, CLCN2, SCN11A, NLRP3, IDH1, RIT1, TRIO, ADCY5, DNM2, SCN1B, SLC26A2, SCN8A, ALG1, KCNJ11, CHRNA1, MAP2K2, IFIH1, ACAD9, PKP2, CACNA1C, ORC1, UBTF, C3, KRAS, FANCA, FGF12, TIA1, HOXD13, CHRNB2, PSEN2, ACADM, MPL, SCN1A, GLMN, NRAS, RARB, PRKAR1A, SOS1, PCGF2, CACNA1E, PIK3CD or F5. [0471] Embodiment 40. The method of any one of embodiments 33-39, wherein the population of cells is a eukaryotic population of cells, a mammalian population of cells, an insect population of cells, a human population of cells or a plant population of cells. [0472] Embodiment 41. A modified population of cells produced by any one of the methods of embodiments 33-40. [0473] Embodiment 42. A method of reducing or eliminating the expression of a gene product in a subject comprising introducing to a cell of a subject the vector of any one of embodiments 19-25, the viral particle of any one of embodiments 26-28, the population of embodiment 29 or the pharmaceutical composition of embodiment 30. [0474] Embodiment 43. A method for treating or alleviating a symptom of a gene product related disorder in a subject comprising the step of introducing to a cell of the subject the vector of any one of embodiments 19-25, the viral particle of any one of embodiments 26- 28, the population of embodiment 29 or the pharmaceutical composition of embodiment 30. [0475] Embodiment 44. The method of embodiment 42 or 43, wherein the subject is a human.