Inventors:
- Cambridge MA, US
Jonathan Wilde - Cambridge MA, US
Tomomi Aida - Arlington MA, US
Martin Wienisch - Arlington MA, US
Assignee:
Massachusetts Institute of Technology - Cambridge MA
International Classification:
C12N 15/90
C12N 9/22
C12N 15/113
A61K 31/136
C12N 15/877
C12N 5/073
A01K 67/027
A61K 35/54
Abstract:
Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.