Publication number: 20190010517
Abstract: Compositions and methods are provided for inducing/enhancing homologous recombination (HR) in a target cell (e.g., for editing a genome). In some embodiments, a subject method includes introducing into a cell: (a) a donor DNA (e.g., via a virus such as AAV); and (b) an agent that inhibits expression and/or function of an endogenous gene (e.g., an RNAi agent, a genome editing agent, a chemical inhibitor). In some cases, the endogenous gene is selected from: FANCM, DDX28, PCBP1, SFRS1/SRSF1, CDK19, DNAJA3/TID1, CDC16, CDT1, SASS6, SPC24, CENPM, MCM2, KLHL9, MYBBP1A, NUP85, NUP88, KIF4A, MASTL, CRLF3, SET, GABPB1, PSMB4, THAP6, COPZ1, RMI1, BLM, TOP3A, and RM12. In some embodiments, a subject method includes introducing into a target cell: (a) a donor DNA (e.g., via a virus such as AAV); and (b) an agent that inhibits centriole/centrosome assembly (e.g., an inhibitor of Polo-like kinase 4 (Plk4), centrinone, centrinone B, CFI-400945, R1530, and the like).
Type:
Application
Filed:
June 29, 2018
Publication date:
January 10, 2019
Inventors:
Mark A. Kay, Gustavo De Alencastro