US 12,441,814 B2
Compositions and methods for enhancing donor oligonucleotide-based gene editing
Elias Quijano, Durham, CT (US); Audrey Turchick, Chelmsford, MA (US); and Peter Glazer, Guilford, CT (US)
Assigned to YALE UNIVERSITY, New Haven, CT (US)
Appl. No. 17/272,136
Filed by Yale University, New Haven, CT (US)
PCT Filed Aug. 30, 2019, PCT No. PCT/US2019/048953
§ 371(c)(1), (2) Date Feb. 26, 2021,
PCT Pub. No. WO2020/047344, PCT Pub. Date Mar. 5, 2020.
Claims priority of provisional application 62/725,920, filed on Aug. 31, 2018.
Prior Publication US 2021/0340280 A1, Nov. 4, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/44 (2006.01); A61K 31/7088 (2006.01); A61K 35/14 (2015.01); A61K 39/00 (2006.01); A61K 47/69 (2017.01); A61K 48/00 (2006.01); A61P 43/00 (2006.01); C07K 16/40 (2006.01); C12N 15/10 (2006.01); C12N 15/11 (2006.01)
CPC C07K 16/44 (2013.01) [A61K 31/7088 (2013.01); A61K 35/14 (2013.01); A61K 47/6937 (2017.08); A61K 48/0008 (2013.01); A61P 43/00 (2018.01); C12N 15/102 (2013.01); C12N 15/11 (2013.01); A61K 2039/505 (2013.01); C07K 16/40 (2013.01); C07K 2317/622 (2013.01); C07K 2317/626 (2013.01); C07K 2317/77 (2013.01)] 19 Claims
 
1. A method of modifying the genome of a cell comprising contacting the cell with an effective amount of a composition comprising a non-covalent complex comprising:
(i) a donor oligonucleotide comprising a sequence that can correct at least one mutation in the cell's genome; and
(ii) an antibody or an antigen-binding fragment thereof,
wherein the antibody or antigen-binding fragment thereof comprises:
(a) a heavy chain variable region (VH) complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 16,
(b) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 17,
(c) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 18,
(d) a light chain variable region (VL) CDR1 comprising the amino acid sequence of SEQ ID NO: 24,
(e) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 25, and
(f) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 26;
and wherein the composition does not comprise a nuclease, a triplex-forming peptide nucleic acid oligomer, or nanoparticles.