HGENE.016WO PATENT AMPHIPHILIC CATIONIC TERPOLYMERS, PREPARATION AND USES BACKGROUND Field [0001] The present disclosure relates to amphiphilic cationic terpolymers (ACTP) comprising functionalized poly(ethylene glycol) backbones and ester pendant groups. The present disclosure further relates methods of making amphiphilic terpolymers and methods of making mRNA-terpolymer polyplexes having suitable properties for micelle formation and other biocompatible applications. Description of the Related Art [0002] Cationic polymers have been employed commonly as drug delivery agents due to their encapsulation efficacy, enhanced bioavailability, biodegradability, and release profiles. Cationic polymers comprising polyethyleneimine-alt-polyethylene glycol and polyethyleneimine (PEI) backbones have been used for gene delivery (M.R. Park, et al., Journal of Controlled Release 2005, 105, 367–380; Zi-Chen Li, et al., Biomacromolecules 2011, 12, 66–74). However, the use of such polymers may result in cytotoxicity in PEI-mediated cell transfection. First, free PEI can interact with negatively charged serum proteins such as albumin and red blood cells, resulting in the precipitation of these proteins in clusters adhering onto the cells surface. Additionally, PEI may also interact with cellular components and inhibit normal cellular functions. [0003] Others have reported the synthesis of star polymers with a crosslinked core by Atomic Transfer Radical Polymerization (ATRP) for siRNA delivery. H.Y. Cho, et al., Biomacromolecules 2011, 12, 3478–3486; H.Y. Cho, et al., Biomacromolecules 2013, 14, 1262- 1267; C. Boyer, et al., Mol. Pharmaceutics 2013, 10, 2435−2444. These star polymers have a biodegradable core comprising disulfide cross-linkages and dendritic positively charged arms. The preparation of these star polymers relies on multiple-steps syntheses. [0004] K. Lee and S. Maity disclosed the use of β-benzyl aspartic acid to prepare cationic homopolymers and copolymers comprising amide functionality along the polymer backbone. Pendant groups were attached to the backbone by amidization. See International Pat. Pub. No. WO 2020/086910. Using a similar approach, Lee and Maity prepared various cationic copolymers comprising a plurality of repeat units and amide pendants. See International Pat. Pub. Nos. WO 2019/210326, WO 2020/243370, WO 2020/219776, and WO 2021/217082, and U.S. Pat Pub. No. 2021/0238347. However, the polymers described by Lee and Maity rely on amide functionalities to form the polymer backbones and attachment of pendants. Such reliance on amide functionalities may impede biodegradability of the polymers. Moreover, the degradation of the residual polyamides may present cytotoxicity issues. [0005] D.G. Anderson and co-workers have prepared linear cationic homopolymers comprising ester functionalities along the polymer backbone. J.C. Kaczmarek, et al., Angew. Chem. Ins. Ed., 2016, 55, 1-6. However, the polymer backbone also included residual aromatic rings that can give rise to long-term cytotoxicity issues. [0006] Robert Langer and coworkers reported the parallel synthesis and screening of a degradable cationic polymer library in which a primary amine inserted into two vinyl groups of a diacrylate to form a linear homopolymer. “Accelerated Discovery of Synthetic Transfection Vector: Parallel Synthesis and Screening of a Degradable Polymer Library,” David M. Lynn, et al., JACS 2001, 123, 8155-8156; (b) “Semi-Automated Synthesis and Screening of a Large Library of Degradable Cationic Polymers for Gene Delivery,” Daniel G. Anderson, et al., Angew. Chem. Int. Ed. 2003, 42, 3153 – 3158. These cationic homopolymers can be used as transfect vectors for gene delivery. [0007] Others have prepared various types of cationic polymers. However, all of these polymers are linear homopolymers that can have short pendants attached. There have been no reports of polymers comprising different types of repeating units, e.g., hydrophobic units, hydrophilic units, and units with pendant groups. [0008] Accordingly, a need exists for biodegradable polymers with low cytotoxicity that can be safely used in therapeutics. In particular, a need exists for copolymers comprising different types of repeating units that can be prepared and optimized for use in biocompatible applications such as mRNA delivery. SUMMARY [0009] In one aspect of the present disclosure, provided herein is a polymer having repeating units of Formula (Ia), (Ib), and (Ic): , , wherein: R ¹ is H or -(CH ₂ ) _x N(R ^1A )(R ^1B ); R ² is independently -(CH2)yOR ^2A ; R ³ is C2-C30 alkyl or -R ^3A -O-R ^3B ; each of m1, m2 and m3 is independently an integer from 2 to 2000; each R ^1A and R ^1B is independently optionally substituted C1-C6 alkyl; R ^2A is hydrogen, a hydroxy protecting group, or -C(=O)(CH ₂ CH ₂ O) _n CH ₂ CH ₂ OR ⁴ ; R ^3A is C1-C6 alkylene; R ^3B is C ₂ -C ₃₀ alkyl; R ⁴ is optionally substituted C1-C6 alkyl; n is an integer from 2 to 100; and each of x and y is independently an integer from 1 to 20. [0010] In some embodiments, the polymer comprises a structure of Formula (II): O R ³ O R ₁ O N O N s embodiments, each of p, q and s is independently an integer from 50 to 800, or from 100 to 500. [0011] In some embodiments of the polymer of Formula (I) or (II), R ¹ is -(CH2)xN(CH3)2. In some such embodiments, x is from 2 to 10, from 3 to 9, or from 4 to 8. [0012] In some embodiments of the polymer of Formula (I) or (II), y is from 2 to 10, from 3 to 9, or from 4 to 8. In some embodiments, R ^2A is hydrogen. In other embodiments, R ^2A is -C(=O)(CH2CH2O)nCH2CH2OCH3. In some such embodiments, n is an integer from 2 to 60. [0013] In some embodiments of the polymer of Formula (I) or (II), R ³ is C ₂ -C ₂₅ alkyl, C5-C20 alkyl, C7-C15 alkyl, or C8-C12 alkyl. In other embodiments, R ³ is -R ^3A -O-R ^3B , wherein R ^3A is C ₁ -C ₆ alkylene (such as –(CH ₂ ) _1-6 –), and wherein R ^3B is C ₂ -C ₂₅ alkyl, C ₅ -C ₂₀ alkyl or C ₇ -C ₁₅ alkyl. [0014] In some embodiments of the polymer of Formula (I) or (II), each of m1, m2 and m3 is independently an integer from 2 to 1000, from 2 to 500, from 2 to 100, from 4 to 100, from 4 to 50, or from 2 to 60. [0015] In some embodiments of the polymer of Formula (I) or (II), the polymer has an average molecular weight from about 1 kDa to about 5,000 kDa, from about 2 kDa to about 500 kDa, from about 5 kDa to about 100 kDa, or from about 10 kDa to about 50 kDa. In some further embodiments, the polymer has an average molecular weight from about 2 kDa to about 10 kDa. [0016] In some further embodiments of the polymer of Formula (I), R ¹ is -(CH2)3- 6N(CH3)2, R ² is -(CH2)3-6OH, and R ³ is a C8-C12 alkyl. In some further embodiments, the polymer comprises the structure of Formula (IIa): N s a , , , 1), , of: (i) mixing a first solution comprising R ¹ -NH ₂ , HO-(CH ₂ ) _z -NH ₂ , and R ³ -NH ₂ with one or more diacrylate compounds of Formula (IIIa), (IIIb), or (IIIc): (ii) adding a capping agent to the second solution after polymerization is complete to form a polymer solution mixture; (iii) concentrating the polymer solution mixture to form a concentrated polymer solution mixture; and (iv) adding a precipitation solvent to the concentrated polymer solution mixture to precipitate the polymer; wherein each of m1, m2 and m3 is independently an integer from 2 to 2000; R ¹ is H or -(CH2)xN(R ^1A )(R ^1B ); each R ^1A and R ^1B is independently optionally substituted C ₁ -C ₆ alkyl; R ³ is C2-C30 alkyl or -R ^3A -O-R ^3B ; R ^3A is C1-C6 alkylene; R ^3B is C ₂ -C ₃₀ alkyl; and each of x and z is independently an integer from 1 to 20. [0018] In some embodiments of the method described herein, the polymer comprises a structure of Formula (IIb): p, q, s are to z an to [0019] In some embodiments of the method described herein, each of p, q and s is independently an integer from 50 to 800, from 100 to 500, or from 200 to 1000. [0020] In some embodiments of the method described herein, R ¹ is -(CH ₂ ) _x N(CH ₃ ) ₂ . In some such embodiments, x is 2 to 20. In other embodiments, x is 3 to 10. In other embodiments, x is 4 to 8. [0021] In some embodiments of the method described herein, R ³ is C2-C25 alkyl, C5- C ₂₀ alkyl, C ₇ -C ₁₅ alkyl, or C ₈ -C ₁₂ alkyl. In other embodiments, R ³ is -R ^3A -O-R ^3B , wherein R ^3A is C1-C6 alkylene (such as –(CH2)1-6–), and wherein R ^3B is C2-C25 alkyl, C5-C20 alkyl or C7-C15 alkyl. [0022] In some embodiments of the method described herein, each of m1, m2 and m3 is independently an integer from 10 to 60, or from 20 to 200. In some embodiments, m1, m2 and m3 have the same value. [0023] In some embodiments of the method described herein, the first solution comprises or is acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, dichloromethane, dimethoxyethane, or 1,4-dioxane, or a combination thereof. In some embodiments, the first solution comprises tetrahydrofuran or dichloromethane. [0024] In some embodiments of the method described herein, the reaction mixture in the second solution is stirred for a period of about 1 hour to about 24 hours. In other embodiments, the reaction mixture in the second solution is stirred for a period of about from about 2 hours to about 20 hours. [0025] In some embodiments of the method described herein, the reaction mixture in the second solution is stirred at temperature of from about 30 °C to about 70 °C. In other embodiments, the reaction mixture in the second solution is stirred at temperature of from about 40 °C to about 60 °C. In some embodiments, the reaction mixture in the second solution is stirred at temperature of about 50°C. In some other embodiments, the reaction mixture in the second solution is stirred at ambient temperature (e.g., about 20°C to about 30°C, or about 22°C to about 28°C or about 25°C). [0026] In some embodiments of the method described herein, the capping agent comprises or is diethylamine, dimethylamine, piperidine, acrylate, 2-methoxyethylacrylate or pyrrole, or combinations thereof. In one embodiment, the capping agent is dimethylamine. In another embodiment, the capping agent is 2-methoxyethylacrylate. [0027] In some embodiments of the method described herein, the precipitation solvent comprises or is pentane, hexane, heptane, diethyl ether, t-butyl methyl ether, toluene, isopropyl acetate, dichloromethane, ethyl acetate, methanol, ethanol, isopropanol, butanol, or combinations thereof. In some embodiments, the precipitation solvent comprises or is hexane. [0028] In some embodiments of the method described herein, the polymer is further reacted with a compound of Formula (IV) , to form a polymer comprising a repeating unit of , wherein: R ⁴ is , Z ⁺ is a monovalent cation; and n is an integer from 2 to 100. [0029] In some embodiments of the method described herein, the polymer comprises a structure of Formula (IIc): O R ³ O R ₁ O N ^O O N O O _N ^O m3 s [0031] In some embodiments of the method described or . A further aspect of the present disclosure relates to an mRNA polyplex comprising the polymer described herein and one or more mRNA molecules. [0033] Additional aspect of the present disclosure relates to a method of making an mRNA polyplex, comprising: (i) mixing one or more mRNA molecules with the polymer described herein in a buffer solution to form an mRNA polyplex suspension; and (ii) incubating the mRNA polyplex suspension. [0034] In some embodiments of the method of making the mRNA polyplex, the buffer solution has a pH of from about 7.0 to about 8.0. In some embodiments, the buffer solution has a pH of about 7.5. In some embodiments, the buffer solution comprises PBS, HEPES, bis-tris, tris, bicine, PIPES, tris-acetate-EDTA, tris-borate-EDTA, TAPS-EDTA, or combinations thereof. In some embodiments, the buffer solution comprises HEPES. [0035] In some embodiments of the method of making the mRNA polyplex, the concentration of the polymer in the buffer solution is from about 0.1 µg/mL to about 1000 µg/mL, from about 0.2 µg/mL to about 500 µg/mL, or from about 0.5 µg/mL to about 200 µg/mL. [0036] In some embodiments of the method of making the mRNA polyplex, the mRNA polyplex suspension is incubated for a period of about 1 minute to about 60 minutes. In other embodiments, the mRNA polyplex suspension is incubated for a period of from about 10 minutes to about 30 minutes. In some embodiments, the mRNA polyplex suspension is incubated for a period of about 20 minutes. [0037] In some embodiments of the method of making the mRNA polyplex, the mRNA polyplex suspension is incubated at about 0 °C to about 5 °C. [0038] In some embodiments of the method of making the mRNA polyplex, the average particle size of the mRNA polyplex is from about 10 nm to about 200 nm. In other embodiments, the average particle size of the mRNA polyplex is from about 50 nm to about 150 nm. [0039] In some embodiments of the method of making the mRNA polyplex, the zeta potential of the mRNA polyplex is from about +10 mV to about +40 mV. In other embodiments, the zeta potential of the mRNA polyplex is from about +20 mV to about +30 mV. [0040] In any embodiments of the method described herein, the mRNA polyplex is in the form of nanoparticles. DETAILED DESCRIPTION [0041] Cationic polymers have been used as delivery vehicles for DNA and mRNA. Previously prepared cationic polymers often utilized polyethyleneimine and polyamide linkages in the polymer backbones, which can lead to decreased biodegradability and increased cytotoxicity in vivo. Embodiments of the present disclosure relate to amphiphilic cationic terpolymers (ACTP) having three types of repeating units. The ACTPs described herein may comprise (1) repeating hydrophilic units with tertiary amines that can be protonated at physiological pH to carry a positive charge; (2) repeating units bearing hydroxyl groups that enable functionalization with poly(ethylene glycol) pendants via formation of an ester linkage; and (3) repeating units having hydrophobic alkyl groups. The properties of the ACTP polymer may be varied by adjusting the ratios of the repeating units and the length of the poly(ethylene glycol) pendant groups. Also provided herein are methods for making the ACTPs disclosed herein via Michael addition chemistry with a diacrylate having two terminal vinyl groups and three different types of primary amines. Also provided herein is making mRNA-ACTP polymer complexes (mRNA polyplexes) with the ACTPs described herein. The ACTPs described herein can be made effectively with high purity, and methods described herein are user-friendly and amenable to scale-up. Definitions [0042] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. [0043] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art. All patents, applications, published applications and other publications referenced herein are incorporated by reference in their entirety unless stated otherwise. In the event that there are a plurality of definitions for a term herein, those in this section prevail unless stated otherwise. As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Unless otherwise indicated, conventional methods of mass spectroscopy, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques and pharmacology are employed. The use of “or” or “and” means “and/or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “include”, “includes,” and “included,” is not limiting. As used in this specification, whether in a transitional phrase or in the body of the claim, the terms “comprise(s)” and “comprising” are to be interpreted as having an open-ended meaning. That is, the terms are to be interpreted synonymously with the phrases “having at least” or “including at least.” When used in the context of a process, the term “comprising” means that the process includes at least the recited steps, but may include additional steps. When used in the context of a compound, composition, or device, the term “comprising” means that the compound, composition, or device includes at least the recited features or components, but may also include additional features or components. By “consisting of” is meant including, and limited to, whatever follows the phrase “consisting of.” By “consisting essentially of” is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. [0044] As used herein, the term “average molecular weight” is the weight-average molecular weight (Mw) of a sample population made up of polymer species having a multiplicity of molecular weights. This quantity is defined by the equation: where n _i indicates _i M _i is the molecular weight of i ^th species. As used herein, the term “molecular weight” refers to weight average molecular weight, unless otherwise specified. [0045] As used herein, the term “polymer” used herein in its traditional sense, is a large molecule composed of smaller monomeric or oligomeric subunits covalently linked together to form a chain. A “homopolymer” is a polymer made up of only one monomeric repeating unit. A “copolymer” refers to a polymer made up of two or more kinds of monomeric repeating units. A "terpolymer” refers to a polymer made up of three different kinds of monomeric repeating units. Linear polymers are composed of monomeric subunits linked together in one continuous length to form polymer chains. Branched polymers are similar to linear polymers but have side chains protruding from various branch points along the main polymer. Star-shaped polymers are similar to branched polymers except that multiple side branches radiate from a single branch site, resulting in a star-shaped or wheel-and- spoke appearance. [0046] As used herein, “alkyl” refers to a straight or branched hydrocarbon chain that comprises a fully saturated (no double or triple bonds) hydrocarbon group. The alkyl group may have 1 to 20 carbon atoms (whenever it appears herein, a numerical range such as “1 to 20” refers to each integer in the given range; e.g., “1 to 20 carbon atoms” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated). The alkyl group may also be a medium size alkyl having 1 to 10 carbon atoms. The alkyl group could also be a lower alkyl having 1 to 6 carbon atoms. The alkyl group of the compounds may be designated as “C ₁ -C ₄ alkyl” or similar designations. By way of example only, “C1-C4 alkyl” indicates that there are one to four carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl (straight chain or branched), and hexyl (straight chain or branched). The alkyl group may be substituted or unsubstituted. [0047] As used herein, “alkenyl” refers to a straight or branched hydrocarbon chain containing one or more double bonds. The alkenyl group may have 2 to 20 carbon atoms. By way of example only, “C2-C6 alkenyl” indicates that there are two to six carbon atoms in the alkenyl chain, i.e., the alkenyl chain is selected from the group consisting of ethenyl, propen-1-yl, propen- 2-yl, propen-3-yl, buten-1-yl, buten-2-yl, buten-3-yl, buten-4-yl, 1-methyl-propen-1-yl, 2- methyl-propen-1-yl, 1-ethyl-ethen-1-yl, 2-methyl-propen-3-yl, buta-1,3-dienyl, buta-1,2,-dienyl, and buta-1,2-dien-4-yl. Typical alkenyl groups include, but are in no way limited to, ethenyl, propenyl, butenyl, pentenyl, and hexenyl, and the like. The alkenyl group may be substituted or unsubstituted. [0048] As used herein, “alkynyl” refers to a straight or branched hydrocarbon chain containing one or more triple bonds. The alkynyl group may have 2 to 20 carbon atoms. By way of example only, “C2-C 4 alkynyl” indicates that there are two to six carbon atoms in the alkynyl chain, i.e., the alkynyl chain is selected from the group consisting of ethynyl, propyn-1-yl, propyn- 2-yl, butyn-1-yl, butyn-3-yl, butyn-4-yl, and 2-butynyl. Typical alkynyl groups include, but are in no way limited to, ethynyl, propynyl, butynyl, pentynyl, and hexynyl, and the like. The alkynyl group may be substituted or unsubstituted. [0049] As used herein, “cycloalkyl” refers to a completely saturated (no double or triple bonds) mono- or multi- cyclic hydrocarbon ring system. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro fashion. As used herein, the term “fused” refers to two rings which have two atoms and one bond in common. As used herein, the term “bridged cycloalkyl” refers to compounds wherein the cycloalkyl contains a linkage of one or more atoms connecting non-adjacent atoms. As used herein, the term “spiro” refers to two rings which have one atom in common and the two rings are not linked by a bridge. Cycloalkyl groups can contain 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s), or 3 to 6 atoms in the ring(s). A cycloalkyl group may be unsubstituted or substituted. Examples of monocyclic cycloalkyl groups include, but are in no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Examples of bicyclic fused cycloalkyl groups are decahydronaphthalenyl, dodecahydro-1H-phenalenyl and tetradecahydroanthracenyl; examples of bicyclic bridged cycloalkyl groups are bicyclo[1.1.1]pentyl, adamantanyl and norbornanyl; and examples of bicyclic spiro cycloalkyl groups include spiro[3.3]heptane and spiro[4.5]decane. [0050] As used herein, “carbocyclyl” refers to a non-aromatic a mono- or multi- cyclic hydrocarbon ring system. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro fashion, as described herein. Carbocyclyl groups can contain 3 to 30 atoms in the ring(s), 3 to 20 atoms in the ring(s), 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s) or 3 to 6 atoms in the ring(s). A carbocyclyl group may be unsubstituted or substituted. Examples of carbocyclyl groups include, but are in no way limited to, cycloalkyl groups, as defined herein, and the non-aromatic portions of 1,2,3,4-tetrahydronaphthalene, 2,3-dihydro-1H- indene, 5,6,7,8-tetrahydroquinoline and 6,7-dihydro-5H-cyclopenta[b]pyridine. [0051] As used herein, “aryl” refers to a carbocyclic (all carbon) monocyclic or multicyclic aromatic ring system (including fused ring systems where two carbocyclic rings share a chemical bond) that has a fully delocalized pi-electron system throughout all the rings. The number of carbon atoms in an aryl group can vary. For example, the aryl group can be a C6 aryl group, or a C10 aryl group. Examples of aryl groups include, but are not limited to, benzene and naphthalene. An aryl group may be substituted or unsubstituted. [0052] As used herein, “heteroaryl” refers to a monocyclic or multicyclic aromatic ring system (a ring system with fully delocalized pi-electron system) that contain(s) one or more heteroatoms (for example, 1, 2 or 3 heteroatoms), that is, an element other than carbon, including but not limited to, nitrogen, oxygen and sulfur. The number of atoms in the ring(s) of a heteroaryl group can vary. For example, the heteroaryl group can contain 5 to 10 atoms in the ring(s), 6 to 10 atoms in the ring(s) or 5 to 6 atoms in the ring(s), such as nine carbon atoms and one heteroatom; eight carbon atoms and two heteroatoms; seven carbon atoms and three heteroatoms; eight carbon atoms and one heteroatom; seven carbon atoms and two heteroatoms; six carbon atoms and three heteroatoms; five carbon atoms and four heteroatoms; five carbon atoms and one heteroatom; four carbon atoms and two heteroatoms; three carbon atoms and three heteroatoms; four carbon atoms and one heteroatom; three carbon atoms and two heteroatoms; or two carbon atoms and three heteroatoms. Furthermore, the term “heteroaryl” includes fused ring systems where two rings, such as at least one aryl ring and at least one heteroaryl ring or at least two heteroaryl rings, share at least one chemical bond. Examples of heteroaryl rings include, but are not limited to, furan, furazan, thiophene, benzothiophene, phthalazine, pyrrole, oxazole, benzoxazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, thiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, benzothiazole, imidazole, benzimidazole, indole, indazole, pyrazole, benzopyrazole, isoxazole, benzoisoxazole, isothiazole, triazole, benzotriazole, thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, purine, pteridine, quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline and triazine. A heteroaryl group may be substituted or unsubstituted. [0053] As used herein, “heterocyclyl” refers to three-, four-, five-, six-, seven-, eight- , nine-, and ten-membered monocyclic, bicyclic and tricyclic ring system wherein carbon atoms together with from 1 to 5 heteroatoms constitute said ring system. A heterocycle may optionally contain one or more unsaturated bonds situated in such a way, however, that a fully delocalized pi-electron system does not occur throughout all the rings (i.e., heterocyclyl groups are not aromatic). The heteroatom(s) is an element other than carbon including, but not limited to, oxygen, sulfur and nitrogen. A heterocycle may further contain one or more carbonyl functionalities, so as to make the definition include oxo-systems such as lactams, lactones, and cyclic carbamates. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro fashion. As used herein, the term “fused” refers to two rings which have two atoms and one bond in common. As used herein, the term “bridged heterocyclyl” refers to compounds wherein the heterocyclyl contains a linkage of one or more atoms connecting non-adjacent atoms. As used herein, the term “spiro” refers to two rings which have one atom in common and the two rings are not linked by a bridge. Heterocyclyl groups can contain 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s), 3 to 6 atoms in the ring(s), or 5 to 6 atoms in the ring(s). For example, five carbon atoms and one heteroatom; four carbon atoms and two heteroatoms; three carbon atoms and three heteroatoms; four carbon atoms and one heteroatom; three carbon atoms and two heteroatoms; two carbon atoms and three heteroatoms; one carbon atom and four heteroatoms; three carbon atoms and one heteroatom; or two carbon atoms and one heteroatom. Additionally, any nitrogen in a heterocyclyl group may be quaternized. Heterocyclyl groups can be linked to the rest of the molecule via a carbon atom in the heterocyclyl group (C-linked) or by a heteroatom in the heterocyclyl group, such as a nitrogen atom (N-linked). Heterocyclyl groups may be unsubstituted or substituted. Examples of such “heterocyclyl” groups include but are not limited to, aziridine, oxirane, thiirane, azetidine, oxetane, 1,3-dioxin, 1,3-dioxane, 1,4-dioxane, 1,2-dioxolane, 1,3- dioxolane, 1,4-dioxolane, 1,3-oxathiane, 1,4-oxathiin, 1,3-oxathiolane, 1,3-dithiole, 1,3- dithiolane, 1,4-oxathiane, tetrahydro-1,4-thiazine, 2H-1,2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, trioxane, hexahydro-1,3,5-triazine, imidazoline, imidazolidine, isoxazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidine, morpholine, oxirane, piperidine N-oxide, piperidine, piperazine, pyrrolidine, azepane, pyrrolidone, pyrrolidione, 4-piperidone, pyrazoline, pyrazolidine, 2-oxopyrrolidine, tetrahydropyran, 4H-pyran, tetrahydrothiopyran, thiamorpholine, thiamorpholine sulfoxide, thiamorpholine sulfone and their benzo-fused analogs (e.g., benzimidazolidinone, tetrahydroquinoline and/or 3,4-methylenedioxyphenyl). Examples of spiro heterocyclyl groups include 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 2-oxa-6- azaspiro[3.3]heptane, 2,6-diazaspiro[3.3]heptane, 2-oxaspiro[3.4]octane and 2- azaspiro[3.4]octane. [0054] As used herein, “alkylene” refers to a branched, or straight chain fully saturated di-radical chemical group containing only carbon and hydrogen that is attached to the rest of the molecule via two points of attachment. By way of example only, “C _1- C ₁₀ alkylene” indicates that there are one to ten carbon atoms in the alkylene chain. Non-limiting examples include ethylene (-CH ₂ CH ₂ -), propylene (-CH ₂ CH ₂ CH ₂ -), butylene (-CH ₂ CH ₂ CH ₂ CH ₂ -), and pentylene (- CH2CH2CH2CH2CH2-). [0055] As used herein, “alkenylene” refers to a straight or branched chain di-radical chemical group containing only carbon and hydrogen and containing at least one carbon-carbon double bond that is attached to the rest of the molecule via two points of attachment. The alkenylene group may be designated as “C2-C10 alkenylene” or similar designations. By way of example only, “C _2- C ₁₀ alkenylene” indicates that there are two to ten carbon atoms in the alkenylene chain. [0056] As used herein, “alkynylene” refers to a straight or branched chain di-radical chemical group containing only carbon and hydrogen and containing at least one carbon-carbon triple bond that is attached to the rest of the molecule via two points of attachment. The alkynylene group may be designated as “C2-C10 alkenylene” or similar designations. By way of example only, “C2-C10 alkynylene” indicates that there are two to ten carbon atoms in the alkynylene chain. [0057] As used herein, “heteroalkylene” refers to an alkylene group, as defined herein, containing one or more heteroatoms in the carbon back bone (i.e., an alkylene group in which one or more carbon atoms is replaced with a heteroatom, for example, nitrogen atom, oxygen atom or sulfur atom). For example, a -CH2- may be replaced with -O-, -S-, or -NH-. Heteroalkylene groups include, but are not limited to ether, thioether, amino-alkylene, and alkylene-amino-alkylene moieties. In some embodiments, the heteroalkylene may include one, two, three, four, or five - CH ₂ CH ₂ O- unit(s). Alternatively and/or additionally, one or more carbon atoms (for example, a -CH2-) can also be substituted with an oxo (=O) to become a carbonyl -C(=O)-, or be substituted with (=S) to become thiocarbonyl -C(=S)-. [0058] As used herein, “aralkyl” and “(aryl)alkyl” refer to an aryl group, as defined above, connected, as a substituent, via an alkylene group, as described above. The alkylene and aryl group of an aralkyl may be substituted or unsubstituted. Examples include but are not limited to benzyl, 2-phenylalkyl, 3-phenylalkyl, and naphthylalkyl. In some embodiments, the alkylene is an unsubstituted straight chain containing 1, 2, 3, 4, 5, or 6 methylene unit(s). [0059] As used herein, “heteroaralkyl” and “(heteroaryl)alkyl” refer to a heteroaryl group, as defined above, connected, as a substituent, via an alkylene group, as defined above. The alkylene and heteroaryl group of heteroaralkyl may be substituted or unsubstituted. Examples include but are not limited to 2-thienylalkyl, 3-thienylalkyl, furylalkyl, thienylalkyl, pyrrolylalkyl, pyridylalkyl, isoxazolylalkyl, and imidazolylalkyl, and their benzo-fused analogs. In some embodiments, the alkylene is an unsubstituted straight chain containing 1, 2, 3, 4, 5, or 6 methylene unit(s). [0060] As used herein, “(heterocyclyl)alkyl” refer to a heterocyclic or a heterocyclyl group, as defined above, connected, as a substituent, via an alkylene group, as defined above. The alkylene and heterocyclyl groups of a (heterocyclyl)alkyl may be substituted or unsubstituted. Examples include but are not limited to (tetrahydro-2H-pyran-4-yl)methyl, (piperidin-4-yl)ethyl, (piperidin-4-yl)propyl, (tetrahydro-2H-thiopyran-4-yl)methyl, and (1,3-thiazinan-4-yl)methyl. In some embodiments, the alkylene is an unsubstituted straight chain containing 1, 2, 3, 4, 5, or 6 methylene unit(s). [0061] As used herein, “cycloalkylalkyl” and “(cycloalkyl)alkyl” refer to a cycloalkyl group (as defined herein) connected, as a substituent, via an alkylene group. Examples include but are not limited to cyclopropylmethyl, cyclobutylmethyl, cyclopentylethyl, and cyclohexylpropyl. In some embodiments, the alkylene is an unsubstituted straight chain containing 1, 2, 3, 4, 5, or 6 methylene unit(s). [0062] As used herein, “alkoxy” refers to the formula –OR wherein R is an alkyl as is defined above, such as “C1-9 alkoxy”, including but not limited to methoxy, ethoxy, n-propoxy, 1- methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy, and the like. [0063] As used herein, “haloalkyl” refers to an alkyl group in which one or more of the hydrogen atoms are replaced by a halogen (e.g., mono-haloalkyl, di-haloalkyl, and tri- haloalkyl). Such groups include but are not limited to, chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl and 1-chloro-2-fluoromethyl, 2-fluoroisobutyl. A haloalkyl may be substituted or unsubstituted. [0064] As used herein, “haloalkoxy” refers to an alkoxy group in which one or more of the hydrogen atoms are replaced by a halogen (e.g., mono-haloalkoxy, di-haloalkoxy and tri- haloalkoxy). Such groups include but are not limited to, chloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy and 1-chloro-2-fluoromethoxy, 2-fluoroisobutoxy. A haloalkoxy may be substituted or unsubstituted. [0065] As used herein, “amino” refer to a –NH2 group. The term “mono-substituted amino group” as used herein refers to an amino (–NH ₂ ) group where one of the hydrogen atom is replaced by a substituent. The term “di-substituted amino group” as used herein refers to an amino (–NH ₂ ) group where each of the two hydrogen atoms is replaced by a substituent. The term “optionally substituted amino,” as used herein refer to a -NRARB group where RA and RB are independently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, aralkyl, or heterocyclyl(alkyl), as defined herein. [0066] As used herein, “alkylamino” or “(alkyl)amino” refers to a -NRARB group where R _A and R _B are hydrogen or alkyl as defined above, and at least one of R _A and R _B is alkyl. The alkyl portion of the (alkyl)amine, includes, for example, C1-C6 alkyl groups. [0067] As used herein, “aminoalkyl” or “(amino)alkyl” refers to an alkyl group in which one or more of the hydrogen atoms are replaced by an amino group or “-NRARB” group as defined herein. The alkyl portion of the aminoalkyl, includes, for example, C ₁ -C ₆ alkyl. [0068] The term “halogen atom” or “halogen” as used herein, means any one of the radio-stable atoms of column 7 of the Periodic Table of the Elements, such as, fluorine, chlorine, bromine, and iodine. [0069] As used herein, “alkoxyalkyl” or “(alkoxy)alkyl” refers to an alkoxy group connected via an alkylene group, such as C2-C8 alkoxyalkyl, or (C1-C6 alkoxy)C1-C6 alkyl, for example, –(CH2)1-3-OCH3. [0070] As used herein, “-O-alkoxyalkyl” or “-O-(alkoxy)alkyl” refers to an alkoxy group connected via an –O-(alkylene) group, such as –O-(C1-C6 alkoxy)C1-C6 alkyl, for example, –O-(CH2)1-3-OCH3. [0071] As used herein, “aryloxy” and “arylthio” refers to RO- and RS-, in which R is an aryl, as defined above, such as but not limited to phenyl. Both an aryloxy and arylthio may be substituted or unsubstituted. [0072] A “sulfenyl” group refers to an “-SR” group in which R can be hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl, heterocyclyl, aralkyl, or heterocyclyl(alkyl), as defined above. A sulfenyl may be substituted or unsubstituted. [0073] A “sulfinyl” group refers to an “-S(=O)-R” group in which R can be the same as defined with respect to sulfenyl. A sulfinyl may be substituted or unsubstituted. [0074] A “sulfonyl” group refers to an “SO2R” group in which R can be the same as defined with respect to sulfenyl. A sulfonyl may be substituted or unsubstituted. [0075] An “O-carboxy” group refers to a “RC(=O)O-” group in which R can be hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl, heterocyclyl, aralkyl, or heterocyclyl(alkyl), as defined herein. An O-carboxy may be substituted or unsubstituted. [0076] The terms “ester” and “C-carboxy” refer to a “-C(=O)OR” group in which R can be the same as defined with respect to O-carboxy. An ester or C-carboxy may be substituted or unsubstituted. [0077] A “trihalomethanesulfonyl” group refers to an “X ₃ CSO ₂ -“group wherein X is a halogen. [0078] A “trihalomethanesulfonamido” group refers to an “X ₃ CS(O) ₂ N(R)-” group wherein X is a halogen and R is be hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl, heterocyclyl, aralkyl, or heterocyclyl(alkyl), as defined herein. [0079] A “mercapto” group refers to an “-SH” group. [0080] An “S-sulfonamido” group refers to a “-SO2N(RARB)” group in which RA and R _B can be independently hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl, heterocyclyl, aralkyl, or heterocyclyl(alkyl) as defined herein. An S-sulfonamido may be substituted or unsubstituted. [0081] An “N-sulfonamido” group refers to a “RSO2N(RA)-“ group in which R and R _A can be independently hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl, heterocyclyl, aralkyl, or heterocyclyl(alkyl), as defined herein. An N-sulfonamido may be substituted or unsubstituted. [0082] An “O-carbamyl” group refers to a “-OC(=O)N(RARB)” group in which RA and RB can be the same as defined with respect to S-sulfonamido. An O-carbamyl may be substituted or unsubstituted. [0083] An “N-carbamyl” group refers to an “ROC(=O)N(RA) -“ group in which R and RA can be the same as defined with respect to N-sulfonamido. An N-carbamyl may be substituted or unsubstituted. [0084] An “O-thiocarbamyl” group refers to a “-OC(=S)-N(R _A R _B )” group in which RA and RB can be the same as defined with respect to S-sulfonamido. An O-thiocarbamyl may be substituted or unsubstituted. [0085] An “N-thiocarbamyl” group refers to an “ROC(=S)N(RA)-“ group in which R and R _A can be the same as defined with respect to N-sulfonamido. An N-thiocarbamyl may be substituted or unsubstituted. [0086] A “C-amido” group refers to a “-C(=O)N(RARB)” group in which RA and RB can be the same as defined with respect to S-sulfonamido. A C-amido may be substituted or unsubstituted. [0087] An “N-amido” group refers to a “RC(=O)N(RA)-“ group in which R and RA can be the same as defined with respect to N-sulfonamido. An N-amido may be substituted or unsubstituted. [0088] Where the numbers of substituents is not specified (e.g., haloalkyl), there may be one or more substituents present. For example, “haloalkyl” may include one or more of the same or different halogens. [0089] It is understood that, in any compound described herein having one or more chiral centers, if an absolute stereochemistry is not expressly indicated, then each center may independently be of R-configuration or S-configuration or a mixture thereof. Thus, the compounds provided herein may be enantiomerically pure, enantiomerically enriched, or may be stereoisomeric mixtures, and include all diastereomeric, and enantiomeric forms. In addition, it is understood that, in any compound described herein having one or more double bond(s) generating geometrical isomers that can be defined as E or Z, each double bond may independently be E or Z a mixture thereof. Stereoisomers are obtained, if desired, by methods such as, stereoselective synthesis and/or the separation of stereoisomers by chiral chromatographic columns. Likewise, it is understood that, in any compound described, all tautomeric forms are also intended to be included. [0090] Wherever a substituent is depicted as a di-radical (i.e., has two points of attachment to the rest of the molecule), it is to be understood that the substituent can be attached in any directional configuration unless otherwise indicated. Thus, for example, a substituent depicted as –AE– or includes the substituent being oriented such that the A is attached at the leftmost of the molecule as well as the case in which A is attached at the rightmost attachment point of the molecule. In addition, if a group or substituent is depicted as , and when L is defined as a bond or absent; such group or substituent is equivalent . It is to be understood that where compounds disclosed herein have unfilled valencies, then the valencies are to be filled with hydrogens and/or deuteriums. [0092] It is understood that the compounds described herein can be labeled isotopically or by another other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels. Substitution with isotopes such as deuterium may afford certain therapeutic advantages from greater metabolic stability, such as, for example, increased in vivo half-life or reduced dosage requirements. Each chemical element as represented in a compound structure may include any isotope of said element. For example, in a compound structure a hydrogen atom may be explicitly disclosed or understood to be present in the compound. At any position of the compound that a hydrogen atom may be present, the hydrogen atom can be any isotope of hydrogen, including but not limited to hydrogen- 1 (protium), hydrogen-2 (deuterium), and hydrogen-3 (tritium). Thus, reference herein to a compound encompasses all potential isotopic forms unless the context clearly dictates otherwise. [0093] It is understood that the methods and formulations described herein include the use of crystalline forms, amorphous phases, and/or pharmaceutically acceptable salts, solvates, hydrates, and conformers of compounds of preferred embodiments, as well as metabolites and active metabolites of these compounds having the same type of activity. A conformer is a structure that is a conformational isomer. Conformational isomerism is the phenomenon of molecules with the same structural formula but different conformations (conformers) of atoms about a rotating bond. In specific embodiments, the compounds described herein exist in solvated forms with pharmaceutically acceptable solvents such as water, ethanol, or the like. In other embodiments, the compounds described herein exist in unsolvated form. Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent, and may be formed during the process of crystallization with pharmaceutically acceptable solvents such as water, ethanol, or the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. In addition, the compounds provided herein can exist in unsolvated as well as solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein. Other forms in which the compounds of preferred embodiments can be provided include amorphous forms, milled forms and nano- particulate forms. [0094] Likewise, it is understood that the compounds described herein, such as compounds of preferred embodiments, include the compound in any of the forms described herein (e.g., pharmaceutically acceptable salts, crystalline forms, amorphous form, solvated forms, enantiomeric forms, tautomeric forms, and the like). [0095] As used herein, the abbreviations for any protective groups, amino acids and other compounds, are, unless indicated otherwise, in accord with their common usage, recognized abbreviations, or the IUPAC-IUB Commission on Biochemical Nomenclature (See, Biochem. 11:942-944 (1972)). [0096] The terms “protecting group” and “protecting groups” as used herein refer to any atom or group of atoms that is added to a molecule in order to prevent existing groups in the molecule from undergoing unwanted chemical reactions. Examples of protecting group moieties are described in T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3. Ed. John Wiley & Sons, 1999, and in J.F.W. McOmie, Protective Groups in Organic Chemistry Plenum Press, 1973, both of which are hereby incorporated by reference for the limited purpose of disclosing suitable protecting groups. The protecting group moiety may be chosen in such a way, that they are stable to certain reaction conditions and readily removed at a convenient stage using methodology known from the art. A non-limiting list of protecting groups include benzyl (Bn); substituted benzyl; alkylcarbonyls (e.g., t-butoxycarbonyl (BOC), acetyl (i.e., -C(=O)CH3 or Ac), or isobutyryl (iBu); arylalkylcarbonyls (e.g., benzyloxycarbonyl or benzoyl (i.e., - C(=O)Ph or Bz)); substituted methyl ether (e.g., methoxymethyl ether (MOM)); substituted ethyl ether (e,g,, methoxyethyl ether (MOE); a substituted benzyl ether; tetrahydropyranyl ether; silyl ethers (e.g., trimethylsilyl (TMS), triethylsilyl, triisopropylsilyl, t-butyldimethylsilyl (TBDMS), tri-iso-propylsilyloxymethyl (TOM), or t-butyldiphenylsilyl); esters (e.g., benzoate ester); carbonates (e.g., methoxymethylcarbonate); sulfonates (e.g., tosylate or mesylate); acyclic ketal (e.g., dimethyl acetal); cyclic ketals (e.g., 1,3-dioxane or 1,3-dioxolanes); acyclic acetal; cyclic acetal; acyclic hemiacetal; cyclic hemiacetal; cyclic dithioketals (e.g., 1,3-dithiane or 1,3- dithiolane); and triarylmethyl groups (e.g., trityl; monomethoxytrityl (MMTr); 4,4’- dimethoxytrityl (DMTr); or 4,4’,4”-trimethoxytrityl (TMTr)). [0097] The term “leaving group” as used herein refers to any atom or moiety that is capable of being displaced by another atom or moiety in a chemical reaction. More specifically, in some embodiments, “leaving group” refers to the atom or moiety that is displaced in a nucleophilic substitution reaction. In some embodiments, “leaving groups” are any atoms or moieties that are conjugate bases of strong acids. Examples of suitable leaving groups include, but are not limited to, tosylates and halogens. Non-limiting characteristics and examples of leaving groups can be found, for example in Organic Chemistry, 2d ed., Francis Carey (1992), pages 328-331; Introduction to Organic Chemistry, 2d ed., Andrew Streitwieser and Clayton Heathcock (1981), pages 169-171; and Organic Chemistry, 5 ^th ed., John McMurry (2000), pages 398 and 408; all of which are incorporated herein by reference for the limited purpose of disclosing characteristics and examples of leaving groups. [0098] The term “pharmaceutically acceptable salt” as used herein is a broad term, and is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and refers without limitation to a salt of a compound that does not cause significant irritation to an organism to which it is administered and does not abrogate the biological activity and properties of the compound. In some embodiments, the salt is an acid addition salt of the compound. Pharmaceutical salts can be obtained by reacting a compound with inorganic acids such as hydrohalic acid (e.g., hydrochloric acid or hydrobromic acid), sulfuric acid, nitric acid, and phosphoric acid. Pharmaceutical salts can also be obtained by reacting a compound with an organic acid such as aliphatic or aromatic carboxylic or sulfonic acids, for example formic acid, acetic acid (AcOH), propionic acid, glycolic acid, pyruvic acid, malonic acid, maleic acid, fumaric acid, trifluoroacetic acid (TFA), benzoic acid, cinnamic acid, mandelic acid, succinic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, nicotinic acid, methanesulfonic acid, ethanesulfonic acid, p-toluensulfonic acid, salicylic acid, stearic acid, muconic acid, butyric acid, phenylacetic acid, phenylbutyric acid, valproic acid, 1,2- ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2- naphthalenesulfonic acid, or naphthalenesulfonic acid. Pharmaceutical salts can also be obtained by reacting a compound with a base to form a salt such as an ammonium salt, an alkali metal salt, such as a lithium, sodium or a potassium salt, an alkaline earth metal salt, such as a calcium, magnesium or aluminum salt, a salt of organic bases such as dicyclohexylamine, N-methyl-D- glucamine, tris(hydroxymethyl)methylamine, (C ₁ -C ₇ alkyl)amine, cyclohexylamine, dicyclohexylamine, triethanolamine, ethylenediamine, ethanolamine, diethanolamine, triethanolamine, tromethamine, and salts with amino acids such as arginine and lysine; or a salt of an inorganic base, such as aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, or the like. [0099] As used herein, a “nucleotide” includes a nitrogen containing heterocyclic base, a sugar, and one or more phosphate groups. They are monomeric units of a nucleic acid sequence. In RNA, the sugar is a ribose, and in DNA a deoxyribose, i.e. a sugar lacking a hydroxyl group that is present in ribose. The nitrogen containing heterocyclic base can be purine or pyrimidine base. Purine bases include adenine (A) and guanine (G), and modified derivatives or analogs thereof, such as deazapurine. Pyrimidine bases include cytosine (C), thymine (T), and uracil (U), and modified derivatives or analogs thereof. The C-1 atom of deoxyribose is bonded to N-1 of a pyrimidine or N-9 of a purine. [0100] As used herein, a “nucleoside” is structurally similar to a nucleotide, but is missing the phosphate moieties. An example of a nucleoside analogue would be one in which the label is linked to the base and there is no phosphate group attached to the sugar molecule. The term “nucleoside” is used herein in its ordinary sense as understood by those skilled in the art. Examples include, but are not limited to, a ribonucleoside comprising a ribose moiety and a deoxyribonucleoside comprising a deoxyribose moiety. A modified pentose moiety is a pentose moiety in which an oxygen atom has been replaced with a carbon and/or a carbon has been replaced with a sulfur or an oxygen atom. A “nucleoside” is a monomer that can have a substituted base and/or sugar moiety. Additionally, a nucleoside can be incorporated into larger DNA and/or RNA polymers and oligomers. [0101] The term “purine base” is used herein in its ordinary sense as understood by those skilled in the art, and includes its tautomers. Similarly, the term “pyrimidine base” is used herein in its ordinary sense as understood by those skilled in the art, and includes its tautomers. A non-limiting list of optionally substituted purine-bases includes purine, deazapurine, 7- deazapurine, adenine, 7-deaza adenine, guanine, 7-deaza guanine, hypoxanthine, xanthine, alloxanthine, 7-alkylguanine (e.g. 7-methylguanine), theobromine, caffeine, uric acid and isoguanine. Examples of pyrimidine bases include, but are not limited to, cytosine, thymine, uracil, 5,6-dihydrouracil and 5-alkylcytosine (e.g., 5-methylcytosine). [0102] As used herein, “derivative” or “analogue” means a synthetic nucleoside or nucleotide derivative having modified base moieties and/or modified sugar moieties. Such derivatives and analogs are discussed in, e.g., Scheit, Nucleotide Analogs (John Wiley & Son, 1980) and Uhlman et al., Chemical Reviews 90:543-584, 1990. Nucleotide analogs can also comprise modified phosphodiester linkages, including phosphorothioate, phosphorodithioate, alkyl-phosphonate, phosphoranilidate, phosphoramidite, and phosphoramidate linkages. “Derivative” and “analog” as used herein, may be used interchangeably, and are encompassed by the terms “nucleotide” and “nucleoside” defined herein. [0103] As used herein, the term “phosphate” is used in its ordinary sense as understood OH O P O by those skilled in the art, and includes its protonated forms (for and OH used herein, the terms “monophosphate,” “diphosphate,” and “triphosphate” sense as understood by those skilled in the art, and include protonated forms. Amphiphilic Cationic Terpolymers [0104] Several aspects of the present application relate to amphiphilic cationic terpolymers (ACTPs) for use in biological applications such as micelle formation and delivery of a variety of therapeutics, e.g., mRNA delivery. The ACTPs described herein are polymeric surfactants having hydrophilic water-soluble repeating units and hydrophobic water-insoluble repeating units. The ACTPs described herein have backbones comprising poly(ethylene glycol) and ester functionalities and can be further functionalized with poly(ethylene glycol) groups via an ester linkage. The critical micelle concentration of the ACTPs in water can be adjusted by adjusting the amount and relative ratios of the repeating units, as well as by adjusting lengths of the poly(ethylene) glycol units in both the polymer backbone and pendant groups. The poly(ethylene glycol) pendants may improve the biocompatibility and effectiveness of transfection. Furthermore, the cationically charged terpolymer having amphiphilic characteristics may facilitate the formation of micelles in 100 nm or less scales. In contrast to amide moiety, the ester linkages along the polymer main chain can be readily hydrolyzed by the enzymes under biophysiological environments to give non-toxic poly(ethylene glycol). Terpolymers Having Repeating Units (Ia), (Ib), and (Ic) [0105] In some embodiments, the polymer described herein is a polymer having repeating units of Formula (Ia), (Ib), and (Ic): , R ³ is C2-C30 alkyl or -R ^3A -O-R ^3B ; each of m1, m2 and m3 is independently an integer from 2 to 2000; each R ^1A and R ^1B is independently optionally substituted C1-C6 alkyl; R ^2A is hydrogen, a hydroxy protecting group, or -C(=O)(CH2CH2O)nCH2CH2OR ⁴ ; R ^3A is C1-C6 alkylene; R ^3B is C2-C30 alkyl; R ⁴ is optionally substituted C ₁ -C ₆ alkyl; n is an integer from 2 to 100; and each of x and y is independently an integer from 1 to 20. [0106] In some embodiments of the polymer described herein, R ¹ is H. In some other embodiments, R ¹ is -(CH ₂ ) _x N(R ^1A )(R ^1B ), and the length of the alkyl chain represented by -(CH ₂ ) _x in the R ¹ substituent may be varied. In some embodiments, x may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, or within a range defined by any two of the aforementioned values. For example, in some embodiments, x is an integer from 1 to 20, 1 to 15, 2 to 20, 4 to 20, 5 to 18, 6 to 16, 10 to 14, 2 to 10, 4 to 10, 3 to 8, or 5 to 10. In some embodiments, R ^1A and R ^1B may independently be optionally substituted alkyl C1-C6 alkyl. For example, R ^1A and R ^1B may independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, fluoromethyl, difluoromethyl, trifluoromethyl, and 2,2,2-trifluoroethyl. In some embodiments, R ^1A and R ^1B are the same. For example, in some embodiments R ^1A and R ^1B can each be methyl. In other embodiments, R ^1A and R ^1B are different. For example, in some embodiments R ^1A can be methyl and R ^1B can be ethyl. [0107] The length of the alkyl chain represented by -(CH ₂ ) _y in the R ² substituent may be varied. In some embodiments, y may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, or within a range defined by any two of the aforementioned values. For example, in some embodiments, y is an integer from 2 to 20, 3 to 18, 6 to 16, 8 to 14, 2 to 10, 4 to 10, or 3 to 8. [0108] In some embodiments of the polymer described herein, R ^2A may be hydrogen. In other embodiments, R ^2A may be a hydroxy protecting group. In some embodiments, R ^2A is -C(=O)(CH ₂ CH ₂ O) _n CH ₂ CH ₂ OR ⁴ and R ⁴ is optionally substituted C ₁ -C ₆ alkyl. In one embodiment, R ⁴ is methyl. The length of the poly(ethylene glycol) can be varied. In some embodiments, when R ^2A is -C(=O)(CH ₂ CH ₂ O) _n CH ₂ CH ₂ OR ⁴ , n is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100, or within a range defined by any two of the aforementioned values. For example, when R ^2A is -C(=O)(CH2CH2O)nCH2CH2OR ⁴ , n is 2 to 100, 3 to 50, 4 to 40, 5 to 30, 10 to 30, 10 to 20, 2 to 10, 2 to 20, 5 to 15, or 4 to 30. [0109] In some embodiments of the polymer described herein, R ³ represents a hydrophobic alkyl chain having 2 to 30 carbons in length (i.e., R ³ is C ₂ -C ₃₀ alkyl). In some embodiments, R ³ may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 carbons in length, or within a range defined by any two of the aforementioned values. In some embodiments, R ³ is C5-C25 alkyl,C5-C20 alkyl, C6-C18 alkyl, C7- C15 alkyl, or C8-C12 alkyl. In other embodiments, R ³ is -R ^3A -O-R ^3B , wherein R ^3A is C1-C6 alkylene (such as –(CH2)1-6–), and wherein R ^3B is C2-C25 alkyl, C5-C20 alkyl, C6-C18 alkyl, C7-C15 alkyl, or C8-C12 alkyl. [0110] The variables m1, m2 and m3 represent the number of poly(ethylene glycol) units in the repeating groups of Formula (Ia), (Ib), and (Ic), respectively. In some embodiments, each of m1, m2 and m3 is independently an integer from 2 to 1000, from 4 to 500, or from 20 to 200. In some embodiments, each of m1, m2 and m3 is independently 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 300, 400, 500, 600, 700, 800, 900 or 1000. For example, in some embodiments, each of m1, m2 and m3 is from 2 to 1000, 2 to 500, 4 to 500, 4 to 200, 4 to 100, 4 to 50, 2 to 60, 4 to 60, 10 to 60, 12 to 50, 15 to 50, 20 to 200, 20 to 100, 20 to 50, or 30 to 80. In some embodiments, m1, m2 and m3 may be the same value. In some embodiments, m1, m2 and m3 may be different values. In some embodiments, two of m1, m2 and m3 may be the same value and the other of m ¹ , m ² and m ³ may be a different value. [0111] In some embodiments of the polymer described herein, R ¹ is -(CH2)3, 4, 5 or ₆ N(CH ₃ ) ₂ , R ² is -(CH ₂ ) _{3, 4, 5, or 6} OH, and R ³ is a C _8, C _9, C _10, C _11, or C ₁₂ alkyl. [0112] In some embodiments, the polymer comprises a structure of Formula (II): R ³ R ₁ O O O N ^O O N , q, s represent , , , respectively, in the polymer of Formula (II). When R ¹ is -(CH2)xN(R ^1A )(R ^1B ), R1 carries a tertiary amine that is positively charged under physiological conditions. The ACTP charge density can be adjusted by the values of p, q and s and their relative ratios. In some embodiments, p, q, and s may be the same value. In some embodiments, p, q, and s may be different values. In some embodiments, two of p, q, and s may be the same value and one of p, q, and s may be a different value. In some embodiments, each of p, q, and s may independently be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990, 1000, or within a range defined by any two of the aforementioned values. For example, in some embodiments, each p, q, and s is independently from about 5 to about 200, from about 30 to about 150, about 40 to about 100, about 50 to about 75, about 10 to about 500, about 30 to about 300, about 50 to about 500, about 100 to about 800, about 50 to 800, about 100 to about 500, about 200 to 1000, or about 10 to about 200. In some further embodiments, the polymer of Formula (II) is also represented by the structure of Formula (IIa): Ia). ving repeating units of Formula (Ia), (Ib), and (Ic), e.g., the polymer of Formula (II) has an average molecular weight from about 1 kDa to about 5,000 kDa, from about 2 kDa to about 500 kDa, from about 5 kDa to about 100 kDa, or from about 10 kDa to about 50 kDa. In some embodiments, the polymer has an average molecular weight of about 1 kDa, 2 kDa, 3 kDa, 4 kDa, 5 kDa, 6 kDa, 7 kDa, 8 kDa, 9 kDa, 10 kDa, 11 kDa, 12 kDa, 13 kDa, 14 kDa, 15 kDa, 16 kDa, 17 kDa, 18 kDa, 19 kDa, or 20 kDa, or a range defined by any two of the preceding values, for example from about 2 kDa to about 10 kDa. Method of Preparing the Terpolymers [0114] Another aspect of the present application relates to a method of making a polymer having repeating units of Formula (Ia), (Ib-1), and (Ic), 1), , the method comprising the steps of: R ¹ -NH2, HO-(CH2)z-NH2, R ³ -NH2, with one or more diacrylate compounds of Formula (IIIa), (IIIb), or (IIIc): to form a second solution; (ii) adding a capping agent to the second solution after polymerization is complete to form a polymer solution mixture; (iii) concentrating the polymer solution mixture; and (iv) adding a precipitation solvent to the concentrated polymer solution mixture to precipitate the polymer; wherein each of m1, m2 and m3 is independently an integer from 2 to 2000; R ¹ is H or -(CH ₂ ) _x N(R ^1A )(R ^1B ); each R ^1A and R ^1B is independently optionally substituted C1-C6 alkyl; R ³ is C ₂ -C ₃₀ alkyl or -R ^3A -O-R ^3B ; R ^3A is C1-C6 alkylene; R ^3B is C ₂ -C ₃₀ alkyl; and each of x and z is independently an integer from 1 to 20 [0115] In some embodiments of the polymer synthesis method described herein, the polymer having repeating units of Formula (Ia), (Ib-1), and (Ic) comprises a structure of Formula (IIb) wherein each of p, q, and s is independently an integer from 1 to 1000; and z is an integer from 2 to 6. [0116] In some embodiments of the polymer synthesis method described herein, R ¹ is H. In other embodiments, R ¹ is -(CH2)xN(R ^1A )(R ^1B ), and the length of the alkyl chain represented by -(CH2)x in the R ¹ substituent may be varied. In some embodiments, x may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, or within a range defined by any two of the aforementioned values. For example, in some embodiments, x is an integer from 1 to 20, 1 to 15, 2 to 20, 4 to 20, 5 to 18, 6 to 16, 10 to 14, 2 to 10, 4 to 10, 3 to 8, or 5 to 10. In some embodiments, R ^1A and R ^1B may independently be optionally substituted alkyl C1-C6 alkyl. For example, R ^1A and R ^1B may independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n- pentyl, isopentyl, fluoromethyl, difluoromethyl, trifluoromethyl, and 2,2,2-trifluoroethyl. In some embodiments, R ^1A and R ^1B are the same. For example, in some embodiments R ^1A and R ^1B can each be methyl. In other embodiments, R ^1A and R ^1B are different. For example, in some embodiments R ^1A can be methyl and R ^1B can be ethyl. In some embodiments, R ¹ is -(CH2)xN(CH3)2, which is a precursor of protonated amine. [0117] The length of the alkyl chain in repeating unit of Formula (Ib-1) is represented by z. In some embodiments, z may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, or within a range defined by any two of the aforementioned values. For example, in some embodiments, z is an integer from 2 to 20, 4 to 18, 6 to 16, 8 to 14, 2 to 10, 4 to 10, 2 to 6, or 3 to 8. [0118] In some embodiments of the polymer synthesis method described herein, R ³ represents a hydrophobic alkyl chain having 5 to 30 carbons in length (i.e., R ³ is C ₂ -C ₃₀ alkyl). In some embodiments, R ³ may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 carbons in length, or within a range defined by any two of the aforementioned values. In some embodiments, R ³ is C5-C25 alkyl,C5-C20 alkyl or C7-C15 alkyl. In other embodiments, R ³ is -R ^3A -O-R ^3B , wherein R ^3A is C ₁ -C ₆ alkylene (such as –(CH ₂ ) _1-6 –), and wherein R ^3B is C2-C25 alkyl, C5-C20 alkyl or C7-C15 alkyl. [0119] The compound of Formula (IIIa), (IIIb), and (IIIc) are poly(ethylene glycol) diacrylates having two terminal vinyl groups which react with amines, e.g., R ¹ -NH2, HO-(CH2)z- NH2, and R ³ -NH2, via a Michael addition reaction, resulting in a terpolymer having three different types of repeat units. The backbone of the terpolymer comprises biodegradable PEGylated esters. The length of the poly(ethylene glycol) units may be varied, and are represented by the variables m1, m2 and m3. In some embodiments, each of m1, m2 and m3 is independently an integer from 4 to 100. In some embodiments, each of m1, m2 and m3 is independently 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 300, 400, 500, 600, 700, 800, 900 or 10000, or within a range defined by any two of the aforementioned values. For example, in some embodiments, each of m1, m2 and m3 is from about 2 to about 200, about 2 to about 100, about 4 to about 100, about 4 to about 50, about 2 to about 60, about 4 to about 60, about 10 to about 60, about 12 to about 50, about 15 to about 50, about 20 to about 50, or about 30 to about 80. In some embodiments, m1, m2 and m3 may be the same value. In some embodiments, m1, m2 and m3 may be different values. In some embodiments, two of m1, m2 and m3 may be the same value and the other of m1, m2 and m3 may be a different value. [0120] Preparation of a polymer having repeating units of Formula (Ia), (Ib-1), and (Ic) is achieved by mixing a first solution comprising R ¹ -NH ₂ , HO-(CH ₂ ) _z -NH ₂ , and R ³ -NH ₂ with one or more diacrylate compounds of Formula (IIIa), (IIIb), (IIIc) to form a second solution. In some embodiments, the first solution comprises acetonitrile, tetrahydrofuran, 2- methyltetrahydrofuran, dichloromethane, dimethoxyethane, 1,4-dioxane, or a combination thereof. In some specific embodiments, the first solution comprises tetrahydrofuran. In other specific embodiments, the first solvent comprises dichloromethane. In some further embodiments, the polymerization reaction of the monomers is catalyzed by a catalyst. In one embodiment, the catalyst is diazabicycloundecene (DBU). [0121] In some embodiments, the reaction mixture in second solution may be stirred for a period of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours or more, or within a range defined by any two of the aforementioned values. For example, the reaction mixture in the second solution may be stirred for a period of about 1 hour to about 24 hours, or about 2 hours to about 20 hours, or about 3 hours to about 18 hours, or about 5 hours to about 24 hours, or about 10 hours to about 20 hours. The reaction mixture in the second solution may be stirred at room temperature, or the first solution may be stirred at about 20 ˚C, 25 ˚C 30 ˚C, 35 ˚C, 40 ˚C, 45 ˚C, 50 ˚C, 55 ˚C, 60 ˚C, 65 ˚C, 70 ˚C, 75 ˚C, 80 ˚C, 85 ˚C, 90 ˚C, within a range defined by any two of the aforementioned temperatures. For example, the reaction mixture in the second solution may be stirred at a temperature of from about 30 ˚C to about 70 ˚C, or about 40 ˚C to about 60 ˚C. In some further embodiments, the reaction mixture in the second solution is stirred at ambient temperature. [0122] In some embodiments, the polymerization reaction may be quenched by the addition of a capping agent to form a polymer solution mixture. Adding the capping agent is necessary to prevent further reaction of the ends containing an acrylate and an amine. Such side reaction may lead the formation of side products, e.g., oligomers, cyclic polymers. Such side products may increase the polydispersity and affect the expected properties of the desired polymer. Capping agents include, but are not limited to, secondary amines and vinyl compounds (such as acrylates). In some embodiments, the capping agent may be a secondary amine. In some embodiments, the capping agent is selected from the group consisting of: diethylamine, dimethylamine, piperidine, and pyrrole. In some specific embodiments, the capping agent is diethylamine. In other embodiments, when there is an excess amount of amine, the capping agent may include one or more acrylates, such as 2-methoxyethylacrylate. [0123] The resulting polymer may be precipitated by adding a precipitation solvent to the polymer solution mixture in order to precipitate solid polymer, which may then be recovered by known techniques (e.g., filtration). The polymer solution mixture may be concentrated prior to the precipitation step. In some embodiments, the precipitation solvent comprises or is pentane, hexane, heptane, diethyl ether, t-butyl methyl ether, toluene, isopropyl acetate, dichloromethane, ethyl acetate, methanol, ethanol, isopropanol, or butanol, or combinations thereof. In some specific embodiments, the precipitation solvent comprises or is hexane. [0124] In some embodiments, the polymer having repeating units of Formula (Ia), (Ib- 1), and (Ic), e.g., polymer comprising a structure of Formula (IIa), is further reacted with a compound of Formula (IV) (IV), to form a polymer comprising a repeating unit of For R ⁴ is , Z ⁺ is a monovalent cation (e.g., Na ⁺ , K ⁺ ); and n is an integer from 2 to 100. [0125] In some embodiments, reacting the polymer having repeating units of Formula (Ia), (Ib-1), and (Ic), e.g., polymer comprising a structure of Formula (IIb), with a compound of Formula (IV) results in the formation of a polymer comprises a structure of Formula (IIc): O ³ O R O R ₁ s [0126] The values of p, q, and s may be controlled to modulate the properties of the polymer. In some embodiments, p, q, and s may be the same value. In some embodiments, p, q, and s may be different values. In some embodiments, two of p, q, and s may be the same value and one of p, q, and s may be a different value. In some embodiments, each of p, q, and s may independently be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990, 1000, or within a range defined by any two of the aforementioned values. For example, in some embodiments, each p, q, and s is independently from about 5 to about 200, from about 30 to about 150, about 40 to about 100, about 50 to about 75, about 10 to about 500, about 30 to about 300, about 50 to about 500, about 100 to about 800, about 50 to 800, about 100 to about 500, about 200 to 1000, or about 10 to about 200. [0127] The compound of Formula (IV) may be a group that facilitates the reaction with the alcohol functionality on repeating unit of Formula (Ib-1) to form an ester bond. In some , . In some specific embodiments, R ⁵ or . In some specifi ⁴ c embodiments, R is methyl. [0129] In some embodiments, n is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100, or within a range defined by any two of the aforementioned values. For example, in some embodiments, n is 2 to 100, 2 to 50, 3 to 50, 4 to 40, 5 to 30, 10 to 30, 10 to 20, 2 to 10, 2 to 20, 2 to 60, 5 to 15, or 4 to 30. [0130] The preparation of the polymer described herein is generally shown in Scheme 1 provided below. Scheme 1 O O O O O O O m ₁ O _m2 O m3 s s Polyplexes of Amphiphilic Cationic Terpolymers (ACTPs) [0131] Several aspects of the present application relate to amphiphilic cationic terpolymers (ACTPs) disclosed herein for use in biological applications such as micelle formation and delivery of a variety of therapeutics, e.g., mRNA delivery. The polyplexes are nanoparticles in an aqueous medium, and can be formed by mixing a polymer described herein with the desired therapeutic (e.g., DNA, mRNA). The formation of the polyplexes is spontaneous and entropically driven, and leads to colloidal assemblies on the order of 100 nm to 200 nm (i.e., forming nanoparticles). Depending on the relative amounts of cationic polymer and DNA used, polyplexes having positive zeta potentials can be formed. In general, positively charged particles are internalized more readily by cells via non-specific endocytosis than particles that are negatively charged or neutral. [0132] In some embodiments, provided herein is a method of making a mRNA-ACTP polyplex, the method comprising the steps of: (i) mixing one or more mRNA molecules with the polymer described herein in a buffer solution to form an mRNA polyplex suspension; and (ii) incubating the mRNA polyplex suspension. The concentration of mRNA in the buffer solution may range from about 0.1 µg/mL to about 500 µg/mL from about 1 µg/mL to about 200 µg/mL, or from about 10 µg/mL to about 100 µg/mL. The concentration of the polymer in the buffer solution may range from about 0.1 µg/mL to about 5000 µg/mL, from about 100 µg/mL to about 2500 µg/mL, from about 500 µg/mL to about 2000 µg/mL, from about 0.1 µg/mL to about 1000 µg/mL, from about 0.2 µg/mL to about 500 µg/mL, or from about 0.5 µg/mL to about 200 µg/mL. In some embodiments, the molar ratio between mRNA and the polymer may range from 1:1 to about 1:100, from about 1:1 to about 1:50, or from about 1:1 to about 1:10. In some embodiments, the weight ratio between mRNA and the polymer may range from 1:1 to about 1:100, from about 1:1 to about 1:50, or from about 1:1 to about 1:10. [0133] The method of making the mRNA-ACTP polyplex described herein may include dissolving one or more mRNA molecules and the polymer described herein in a buffer solution. In some embodiments, the buffer solution may have a pH of about 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0, or within a range defined by any two of the aforementioned pH values. For example, in some embodiments, the pH of the buffer solution may be from about 7.0 to about 8.0, about 7.4 to about 8.0, about or from about 7.5 to about 7.8. In some specific embodiments, the buffer solution has a pH of about 7.5. In some embodiments, the buffer solution comprises PBS, HEPES, bis-tris, tris, bicine, PIPES, tris-acetate-EDTA, tris-borate-EDTA, TAPS-EDTA or combinations thereof. In some embodiments, the buffer solution comprises HEPES. [0134] Upon contacting the mRNA solution with the polymer to form the polyplex suspension, said polyplex suspension may be incubated for a period of time appropriate for achieving formation of the polyplex. The polyplex suspension may be incubated for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes or more, or within a range defined by any two of the afore-mentioned times. For example, the polyplex suspension may be incubated for from about 5 minutes to about 60 minutes, from about 10 minutes to about 30 minutes, or from about 15 to about 25 minutes. In some specific embodiments, the polyplex suspension solution is incubated for about 20 minutes. The polyplex suspension is generally incubated at from about 0 ˚C to about 10 ˚C, or from about 0 ˚C to about 5 ˚C. For example, the polyplex suspension is incubated at about 0 ˚C, 1 ˚C, 2 ˚C, 3 ˚C ¸4 ˚C, 5 ˚C, 6 ˚C, 7 ˚C, 8 ˚C¸ 9 ˚C, or 10 ˚C. [0135] Without being bound be any particular theory, it is generally desirable to prepare mRNA-ACTP polyplexes wherein the average particle size is 200 nm or less. In some embodiments, the particle size of the mRNA-ACTP complexes described herein can be about 10 nm, 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, or 200 nm, or within a range defined by any two of the afore-mentioned values. For example, the mRNA-ACTP polyplex described herein may have an average particle size of from about 10 nm to about 200 nm, from about 50 nm to about 150 nm, or from about 100 nm to about 200 nm. [0136] It is desirable to form polyplexes having positive a zeta potential. Without being bound to any particular theory, polyplexes having a positive zeta potential have properties suitable for biological applications, as particles with positive zeta potential may be more stable in aqueous solution and internalized more readily by cells. In some embodiments, the zeta potential of the polyplexes described herein is about +10 mV, +15 mV, +20 mV, +25 mV, +30 mV, +35 mV, +40 mV, +45 mV, +50 mV, or within a range defined by any two of the afore-mentioned zeta potential values. For example, in some embodiments, the zeta potential of the polyplex is from about +10 mV to about +40 mV, or from about +20 mV to about +40 mV, or from about +15 mV to about +30 mV, or from about +20 mV to about +30 mV. [0137] Additional embodiments of the present application relate to an oligonucleotide prepared by any of the methods described herein. EXAMPLES [0138] Some aspects of the embodiments discussed above are disclosed in further detail in the following examples, which are not in any way intended to limit the scope of the present disclosure. Those in the art will appreciate that many other embodiments also fall within the scope of the compositions, kits and methods of the present application, as is described herein above and in the claims. Example 1. Preparation of amphiphilic cationic terpolymers (ACTPs) General preparation of ACTP [0139] The terpolymer was synthesized via a thermally-activated aza-Michael addition (step-growth polymerization). In a first experiment, the calculated amounts of monomer and solvent as shown in Table 1 were charged into a 100-mL round bottom three-necked flask equipped with a water-cooled condenser, one ground glass stopper, one rubber septum, and a magnetic stir bar. The reaction mixture in the reaction flask is immersed in an oil bath at 80 °C and constantly stirred for two hours. The reaction mixture is cooled to ambient temperature and the solvent (THF or DCM) is removed under reduced pressure. In a second experiment, the calculated amounts of monomers as shown in Table 2 without solvent were charged into a 50-mL round bottom three-necked flask equipped with a water-cooled condenser, one ground glass stopper, one rubber septum, and a magnetic stir bar. The initial experiments were performed through bulk polymerization (no solvent). The reaction mixture in the reaction flask was immersed in an oil bath at 60 °C and constantly stirred for 16 hours. The reaction mixture was then cooled to ambient temperature. The residue was redissolved in minimum amount of THF and then added dropwise into 20 mL and then added dropwise into 20 mL of stirring hexane to precipitate the terpolymer. The terpolymer was then washed three times with 25mL hexanes. The terpolymer was dried under vacuum for two hours before the characterization using proton NMR and size exclusion chromatography. The terpolymer can be prepared with excess diacrylate or excess diamine to prevent side reactions forming oligomers and cyclic polymers. If the terpolymer is synthesized with excess diacrylate, a post-polymerization capping reaction using dimethylamine will be implemented. If the terpolymer is synthesized with excess amine, a post-polymerization capping reaction using 2-methoxyethylacrylate will be done. For the experiment shown in Table 2, the terpolymer(acrylate-end groups) was redissolved in 20mL of dichloromethane and 0.70g (15.5 mmol) of dimethylamine was added. The reaction was stirred at 80 °C for one hour. The reaction mixture was cooled to ambient temperature and the solvent was removed under reduced pressure. The residue was redissolved in minimum amount of solvent and then added dropwise into 50 mL of stirring hexane to precipitate the terpolymer. The terpolymer was then washed three times with 25mL hexanes. The terpolymer was dried under vacuum for two hours before the characterization using proton NMR and size exclusion chromatography. The reaction is further illustrated in Scheme 2. Table Compound Molecular Volume Mass mmol molar eq. dodecylamine 185.35 1.8535 10 20 3-amino-1-propanol 75.11 0.7511 10 20 after transfection. The molar ratios of p, q and r are adjustable to facilitate micelle formation.

Scheme 2. Preparation of ACTPs A, B, C, and D in the presence of a catalyst plus capping agents: O O O n O Reagents and Catalyst Molecular Mass mmol molar eq. ) Table 3: Monomers and solvents for the preparation of ACTP compounds A, B, C and D PEG Reaction ACTP diacrylate, time ^{Solvent Catalyst Mz} PDI Solubility mmol (hours) _(Da)** ** in H ₂ O A 20.0 24 bulk DBU B* 22.0 24 bulk - branched - soluble C 20.0 48 bulk DBU 5,100 1.8 soluble D* 28.5 48 bulk DBU branched - soluble * The preparation of ACTB compound B and D used excess poly(ethylene glycol) diacrylate than the preparation of compounds A and C. **Mz and polydispersity index (PDI) were determined using SEC with THF eluent and polystyrene standards. [0141] Polymer of Formula (X): ¹ H NMR (DMSO) (δ, ppm): 0.83 (CH ₃ R ₃ ), 1.21 (CH ₂ R3), 1.48 (CH2 R2, R3), 2.07 (2H, CH2 backbone R1), 2.37 (2H, CH2N tail R1), 2.63 (2H; CH2N R ₁ , R ₂ , R ₃ ), 3.47 (4H; methylene PEG backbone, CH ₂ R ₂ ), 3.57 (2H, CH ₂ O PEG), 4.08 (2H, methylene PEG). Example 2. Preparation of mRNA-ACTP polyplexes and ACTP cytotoxicity assay Preparation of mRNA [0142] The mRNA encoding enhanced green fluorescent protein (EGFP) was used in the preparation of mRNA-ACTP polyplexes. EGFP is a commonly used direct reporter in mammalian cell culture as it produces bright green fluorescence (emission peak wavelength at 509 nm), which can be observed in cells by fluorescence microscopy or flow cytometry. By using EGFP mRNA as a reporter marker, it can be determined whether the mRNA integrity is compromised during the process of binding to ACTP, transfection into cells, release into the cytoplasm of the cells, and finally translation into EGFP proteins. If the EGFP mRNA integrity is not compromised, a bright green fluorescence signal can be observed inside the cells. [0143] To generate an EGFP mRNA vector, the EGFP DNA template was designed to contain the following elements in the 5’ to 3’ direction: T7 promoter, human beta globin 5’ UTR (untranslated region), open reading frame (ORF) of EGFP, human beta globin 3’ UTR, poly adenosine (100 bp) and BspQI linearization site. The above DNA template is inserted into pUC57 vector and then transformed into E. coli DH5α for bacteria culture and plasmid amplification. The harvested plasmid DNA is linearized by BspQI restriction enzyme and used as a DNA template for IVT. [0144] FIG.1 shows the different components of an EGFP mRNA. The CAP and Poly A tail protect the mRNA from enzymatic degradation and are required for translation to occur. The 5’ and 3’ untranslated regions (UTRs) are needed for post-transcription gene regulation processes. The central EGFP RNA coding sequence is the RNA coding sequence which determines the sequences of amino acids in the EGFP. [0145] The 5’ capped EGFP mRNA with modified nucleotide Cy5-UTP was prepared using a commercially available high yield in vitro transcription (IVT) kit with 1 µg of DNA template. The mRNA was capped at the 5’ end to stabilize the mRNA and to help in later translation. Cy5 is a far-red fluorescent dye and, when incorporated Cy5 to UTP, allows for visualization of mRNA entry into cells during transfection. IVT was performed according to manufacturer recommendation. After mRNA was synthesized, 1 µL of DNase I (2 U/µL) was added into 20 µL of transcription mixture to remove the DNA template by additional incubation at 37℃. Lithium chloride (LiCl) precipitation was performed to purify EGFP mRNA from the IVT reaction mixture. The 5’ capped EGFP mRNA pellet was dissolved in nuclease free water and analyzed using an Agilent BioAnalyzer 2100 for size and purity. The amount of Cy5-UTP in the EGFP mRNA was measured using a spectro-fluorophotometer (Shimadzu). The final EGFP mRNA concentration was then adjusted to 100 µg/mL. [0146] Cytotoxicity assay was done to determine ACTP toxicity. Human Embryonic Kidney 293 (HEK293) cells were used to test ACTP cytotoxicity. Briefly, HEK293 cells were cultured on 96-well plates with 3000 cells per well. HEK293 cells were cultured in low-glucose Dulbecco’s Modified Eagle’s Medium (DMEM), with the supplement of Fetal Bovine Serum (FBS) to a final concentration of 10%. Cells were grown in a humidified incubator at 37℃ and 5% CO2. HEK293 cells were washed twice with PBS; the medium was replaced with medium with varying concentrations of polymer (0.5 µg/mL, 1 µg/mL, 2.5 µg/mL , 5 µg/mL, 10 µg/mL and 20 µg/mL). After 24 hours incubation, the cytotoxicity was evaluated by MTT assay (obtained from Millipore Sigma) following manufacturer’s instruction. [0147] ACTP polymers A, B, C, and D were prepared with chemical structure as shown in Example 1 labeled as Compound (X), according to the procedure in Example 1. The polymers were separately dissolved in sterile water with constant stirring at ambient temperature overnight using a magnetic stirrer. The polymer solutions were filtered using 0.45 µm poly(tetrafluoroethylene) filter (PTFE). [0148] To generate mRNA-ACTP polyplex, 1 µg of purified EGFP mRNA was mixed individually with different ACTPs (A, B, C and D) dissolved in 10 mM HEPES buffer (pH 7.5) at varying concentrations of polymer (0.5 µg/mL, 1 µg/mL, 2.5 µg/mL, 5 µg/mL, 10 µg/mL and 20 µg/mL). The mixture was mixed by pipetting, followed by incubation for 30 minutes at 4℃. mRNA is less stable than dsDNA and might degrade rapidly at ambient temperature. Gel retardation assay was performed to monitor the binding of EGFP mRNA to ACTP and the delay in EGFP mRNA in moving down the RNA gel during electrophoresis suggests the formation of mRNA-ACTP polyplex. The particle size and shape are determined by SYNC (Microtrac MRB). To further confirm the correct formation of polyplex, the mRNA-ACTP polyplex was treated with RNase1 as only EGFP mRNA in the polyplex can be protected from the digestion. RNase 1 hydrolyzes the phosphodiester bond of all four bases of mRNA. After treatment, the mRNA- ACTP complex was run under gel electrophoresis to determine if the mRNA has been hydrolyzed by RNase 1. After RNase1 treatment, an intact and full-length band of the mRNA suggests the formation of polyplex. [0149] Human Embryonic Kidney 293 (HEK293) cells were used for the transfection of Cy5-UTP labelled-eGFP mRNA-ACTP polyplex. Red fluorescence from Cy5-UTP and green fluorescence protein from translated EGFP mRNA in cells were measured to evaluate mRNA- ACTP polyplex transfection and translation efficiency. [0150] HEK 293 cells were cultured as described herein. Twenty-four hours before transfection, cells were seeded into the 12-well cell culture plate with a density of 100,000 cells per well. An aliquot of 10 µL of the EGFP mRNA-ACTP polyplex (1 µg EGFP mRNA in total) is added into the cell culture, followed by 12–18-hour incubation. A common transfection agent, Lipofectamine 2000 (obtained from Thermofisher) will be used to transfect 1 µg EGFP mRNA into cell culture as a positive control. The effectiveness of mRNA-ACTP polyplex transfection can be measured by calculating the percentage of Cy5-UTP labelled EGFP mRNA in cells within a few hours after transfection using EVOS FLoid Imaging system (obtained from Thermofisher). [0151] The ability of mRNA-ACTP polyplex to disassemble once they are inside the cells can be determined by measuring the efficacy of translation of EGFP mRNA in cells. To determine the efficiency of translation of EGFP mRNA, fluorescent microscopy and flow cytometry are performed to detect the green fluorescence in the transfected cells. Fluorescent microscope is used to image cells 12–18-hour after transfection with Cy5-UTP labelled-EGFP mRNA-ACTP polyplex. EGFP expression of adherent HEK293 cells is determine using EVOS Floid Imaging system and Image J software package was used to analyze microscopic images to evaluate transcription and translation effectiveness. For flow cytometry, after trypsinization of adherent HEK 293 cells, cells are harvested by centrifugation at 300xg for 5 min at 4°C. The supernatant will be discarded and 50,000 cells per tube will be resuspend from the cell pellet in 100 µl of Flow Cytometry Staining Buffer (1% bovine serum albumin, 0.1% sodium azide in PBS buffer). Samples are analyzed on a FACScan flow cytometer and a total of 10,000 events is analyzed for each sample. The EGFP fluorescence is collected with a 488 nm filter and data is recorded. All flow cytometric data were analyzed using FlowJo software. The translation efficiency is calculated as the percentage of EGFP-positive cells. Example 3. ACTP binding and capture of dsDNA [0152] ACTP polymers A, B, C, and D were prepared with chemical structure as shown in Example 1 labeled as (X), according to the procedure in Example 1. The polymers were separately dissolved in sterile water with constant stirring at ambient temperature overnight using a magnetic stirrer. The polymer solutions were filtered using 0.45 µm poly(tetrafluoroethylene) filter (PTFE) and no clumps were observed for all four polymers, as shown in FIG. 2. The final concentrations were 100 µg/L (Polymers A and C) and 10 µg/L (Polymers B and D). [0153] Double-stranded DNA (dsDNA) was obtained by performing PCR reactions on DNA plasmid to obtain 1 kb PCR products. To prepare 5 µg/µL final polymer/dsDNA concentration, 10 µL of polymers at 10 µg/µL were mixed with 10 µL dsDNA in water. The total volume was 20 µL. To prepare 2.5 µg/µL final concentration, first 50 µL of polymers at 10 µg/µL were mixed with 50 µL of water to obtain 5 µg/µL concentration. Next, 10 µL of polymers at 5 µg/µL were mixed with 10 µL of dsDNA in water to obtain 2.5 µg/µL final concentration. [0154] The polyplex formation was evaluated using the gel shift assay method. Briefly, the rate of DNA migration down the gel slab will be slower if it is binding to the ACTP relative to if the DNA is unbound. One limitation of the assay is if polymer form large clumps with the DNA, in which case the polymer-DNA clump may be “trapped” in the loading well. Instability of the polymers was observed as less aggregation was found in the loading well after one day and there was no observed aggregation after two days. [0155] Three sets of conditions were employed for evaluation. In Set I, the polymers were incubated with dsDNA for 30 minutes at ambient temperature. In Set II, the polymers were incubated at 37°C before incubating with dsDNA for 30 minutes at ambient temperature, to determine whether pre-warming the polymers would facilitate binding. In Set III, the higher concentrations of polymers A and C were tested with and without incubation at 37°C for 30 minutes before incubating with dsDNA for 30 minutes at ambient temperature, to determine whether higher concentrations of the polymers have an effect on DNA binding. [0156] For Set I, an aliquot of 10 µl polymer was incubated with 1 µg dsDNA for 30 minutes at ambient temperature. Next, 50% of each of the incubated samples were mixed with loading dye. Electrophoresis was performed on 0.7% agarose gel at constant 70V for 1 hour. The results are shown in Fig. 3. It can be observed that at 5 µg/µL concentration, all polymers were bound to the DNA, as seen by the smearing of the DNA on the gel compared to dsDNA by itself (sample 2 in Fig.3), wherein the smearing is indicative of binding. [0157] For Set II, polymers were incubated at 37°C for 30 minutes, then an aliquot of 10 µL of each polymer was incubated with 1 µg dsDNA for 30 minutes at ambient temperature. 50% of each of the incubated samples were mixed with loading dye and electrophoresis was performed on 0.7% agarose gel at constant 70V for 1 hour. The results are shown in FIG.4, which demonstrates that polymers were bound to the dsDNA, indicating polyplex formation, as can be seen by the smearing of the DNA on the gel. Weaker binding than Set I was observed. [0158] For Set III, polymers A and C were tested with and without incubation at 37°C for 30 minutes. An aliquot of 10 µL of polymer solution, with concentration 50 µg/µL was subsequently incubated with 1 µg dsDNA for 30 minutes at ambient temperature.50% of each of the incubated samples were mixed with loading dye and electrophoresis was performed on 0.7% agarose gel at constant 70V for 30 minutes. The results are shown in FIG. 5. The results demonstrate that at 50 µg/µL, polymers A and C bind to dsDNA, with similar smearing regardless of whether they were first incubated at 37°C for 30 minutes. [0159] The interaction of the terpolymers A, B, C and D with digested dsDNA was also characterized. 10 µL each of the polymers at 5 µg/µL concentration, and 0.5µg of dsDNA were incubated at ambient temperature 30 minutes. To the resulting mixture, one unit of DNase1 was added and incubated for 30 minutes at 37°C. The samples were mixed with loading dye and gel electrophoresis was performed on 0.7% agarose gel at constant 70V for 30 minutes. The results are shown in FIG. 6. According to FIG. 6, it was observed that all dsDNA was cleaved/digested by DNase1 and thus, there was no binding of the digested dsDNA by the terpolymers. Example 4. Stability testing of the Amphiphilic Cationic Terpolymers [0160] Tests of the stability of terpolymers A, B, C, and D were also performed. The polymers were dissolved in water and stored at ambient temperature for either one or two days. The polymers were then treated under the same conditions as Set I. The results are shown in FIG. 7, which shows that the polymers in solution began to degrade after one day at ambient temperature.