Title:
COMPOSITIONS FOR ENHANCING TARGETED GENE EDITING AND METHODS OF USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2017/143042
Kind Code:
A3
Abstract:
Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the γ position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications.
Inventors:
SALTZMAN W MARK (US)
GLAZER PETER (US)
BAHAL RAMAN (US)
MCNEER NICOLE ALI (US)
LY DANITH H (US)
QUIJANO ELIAS (US)
GLAZER PETER (US)
BAHAL RAMAN (US)
MCNEER NICOLE ALI (US)
LY DANITH H (US)
QUIJANO ELIAS (US)
Application Number:
PCT/US2017/018142
Publication Date:
October 19, 2017
Filing Date:
February 16, 2017
Export Citation:
Assignee:
UNIV YALE (US)
UNIV CARNEGIE MELLON (US)
UNIV CARNEGIE MELLON (US)
International Classes:
C07K14/00
Domestic Patent References:
| WO2011133803A1 | 2011-10-27 | |||
| WO2010123983A1 | 2010-10-28 |
Other References:
N A MCNEER ET AL: "Systemic delivery of triplex-forming PNA and donor DNA by nanoparticles mediates site-specific genome editing of human hematopoietic cells in vivo", GENE THERAPY, vol. 20, no. 6, 18 October 2012 (2012-10-18), pages 658 - 669, XP055177307, ISSN: 0969-7128, DOI: 10.1038/gt.2012.82
FAYE A. ROGERS ET AL: "Local Delivery of Gene-Modifying Triplex-Forming Molecules to the Epidermis", JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 133, no. 3, 1 March 2013 (2013-03-01), US, pages 685 - 691, XP055376908, ISSN: 0022-202X, DOI: 10.1038/jid.2012.351
HEIKO KUHN ET AL: "Sequence specificity at targeting double-stranded DNA with a gamma-PNA oligomer modified with guanidinium G-clamp nucleobases", ARTIFICIAL DNA: PNA & XNA, vol. 1, no. 1, 1 July 2010 (2010-07-01), pages 45 - 53, XP055376683, ISSN: 1949-095X, DOI: 10.4161/adna.1.1.12444
RAMAN BAHAL ET AL: "Nanoparticle for delivery of antisense [gamma]PNA oligomers targeting CCR5", ARTIFICIAL DNA: PNA & XNA, vol. 4, no. 2, 1 April 2013 (2013-04-01), pages 49 - 57, XP055376890, ISSN: 1949-095X, DOI: 10.4161/adna.25628
BAHAL RAMAN ET AL: "Single-Stranded gamma PNAs for In Vivo Site-Specific Genome Editing via Watson-Crick Recognition", CURRENT GENE THERAPY, BENTHAM SCIENCE PUBLISHERS LTD, NL, vol. 14, no. 5, 1 January 2014 (2014-01-01), pages 331 - 342, XP008184778, ISSN: 1566-5232, DOI: 10.2174/1566523214666140825154158
GUPTA ANISHA ET AL: "Nanotechnology for delivery of peptide nucleic acids (PNAs)", JOURNAL OF CONTROLLED RELEASE, ELSEVIER, AMSTERDAM, NL, vol. 240, 8 January 2016 (2016-01-08), pages 302 - 311, XP029759367, ISSN: 0168-3659, DOI: 10.1016/J.JCONREL.2016.01.005
RAMAN BAHAL ET AL: "In vivo correction of anaemia in [beta]-thalassemic mice by [gamma]PNA-mediated gene editing with nanoparticle delivery", NATURE COMMUNICATIONS, vol. 7, 26 October 2016 (2016-10-26), pages 13304, XP055376685, DOI: 10.1038/ncomms13304
STEVEN LIN ET AL: "Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery", ELIFE, vol. 3, 15 December 2014 (2014-12-15), England, pages e04766, XP055294945, DOI: 10.7554/eLife.04766
NATALIA RIVERA-TORRES ET AL: "The Position of DNA Cleavage by TALENs and Cell Synchronization Influences the Frequency of Gene Editing Directed by Single-Stranded Oligonucleotides", PLOS ONE, vol. 9, no. 5, 1 May 2014 (2014-05-01), pages e96483, XP055394837, DOI: 10.1371/journal.pone.0096483
JINGYUE JIA ET AL: "Bacterial Delivery of TALEN Proteins for Human Genome Editing", PLOS ONE, vol. 9, no. 3, 11 March 2014 (2014-03-11), pages e91547 - 12, XP055394839, DOI: 10.1371/journal.pone.0091547
BRYAN STROUSE ET AL: "Combinatorial gene editing in mammalian cells using ssODNs and TALENs", SCIENTIFIC REPORTS, vol. 4, no. 1, 21 January 2014 (2014-01-21), XP055394840, DOI: 10.1038/srep03791
THOMAS GAJ ET AL: "ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering", TRENDS IN BIOTECHNOLOGY, 1 May 2013 (2013-05-01), XP055065263, ISSN: 0167-7799, DOI: 10.1016/j.tibtech.2013.04.004
FAYE A. ROGERS ET AL: "Local Delivery of Gene-Modifying Triplex-Forming Molecules to the Epidermis", JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 133, no. 3, 1 March 2013 (2013-03-01), US, pages 685 - 691, XP055376908, ISSN: 0022-202X, DOI: 10.1038/jid.2012.351
HEIKO KUHN ET AL: "Sequence specificity at targeting double-stranded DNA with a gamma-PNA oligomer modified with guanidinium G-clamp nucleobases", ARTIFICIAL DNA: PNA & XNA, vol. 1, no. 1, 1 July 2010 (2010-07-01), pages 45 - 53, XP055376683, ISSN: 1949-095X, DOI: 10.4161/adna.1.1.12444
RAMAN BAHAL ET AL: "Nanoparticle for delivery of antisense [gamma]PNA oligomers targeting CCR5", ARTIFICIAL DNA: PNA & XNA, vol. 4, no. 2, 1 April 2013 (2013-04-01), pages 49 - 57, XP055376890, ISSN: 1949-095X, DOI: 10.4161/adna.25628
BAHAL RAMAN ET AL: "Single-Stranded gamma PNAs for In Vivo Site-Specific Genome Editing via Watson-Crick Recognition", CURRENT GENE THERAPY, BENTHAM SCIENCE PUBLISHERS LTD, NL, vol. 14, no. 5, 1 January 2014 (2014-01-01), pages 331 - 342, XP008184778, ISSN: 1566-5232, DOI: 10.2174/1566523214666140825154158
GUPTA ANISHA ET AL: "Nanotechnology for delivery of peptide nucleic acids (PNAs)", JOURNAL OF CONTROLLED RELEASE, ELSEVIER, AMSTERDAM, NL, vol. 240, 8 January 2016 (2016-01-08), pages 302 - 311, XP029759367, ISSN: 0168-3659, DOI: 10.1016/J.JCONREL.2016.01.005
RAMAN BAHAL ET AL: "In vivo correction of anaemia in [beta]-thalassemic mice by [gamma]PNA-mediated gene editing with nanoparticle delivery", NATURE COMMUNICATIONS, vol. 7, 26 October 2016 (2016-10-26), pages 13304, XP055376685, DOI: 10.1038/ncomms13304
STEVEN LIN ET AL: "Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery", ELIFE, vol. 3, 15 December 2014 (2014-12-15), England, pages e04766, XP055294945, DOI: 10.7554/eLife.04766
NATALIA RIVERA-TORRES ET AL: "The Position of DNA Cleavage by TALENs and Cell Synchronization Influences the Frequency of Gene Editing Directed by Single-Stranded Oligonucleotides", PLOS ONE, vol. 9, no. 5, 1 May 2014 (2014-05-01), pages e96483, XP055394837, DOI: 10.1371/journal.pone.0096483
JINGYUE JIA ET AL: "Bacterial Delivery of TALEN Proteins for Human Genome Editing", PLOS ONE, vol. 9, no. 3, 11 March 2014 (2014-03-11), pages e91547 - 12, XP055394839, DOI: 10.1371/journal.pone.0091547
BRYAN STROUSE ET AL: "Combinatorial gene editing in mammalian cells using ssODNs and TALENs", SCIENTIFIC REPORTS, vol. 4, no. 1, 21 January 2014 (2014-01-21), XP055394840, DOI: 10.1038/srep03791
THOMAS GAJ ET AL: "ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering", TRENDS IN BIOTECHNOLOGY, 1 May 2013 (2013-05-01), XP055065263, ISSN: 0167-7799, DOI: 10.1016/j.tibtech.2013.04.004
Attorney, Agent or Firm:
RAYMOND, Adam, S. et al. (US)
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