Targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases
Focal gene amplification is a hallmark of many types of cancer that drives tumorigenesis. Gene amplification represents a potential vulnerability for therapeutic exploitation if DNA damage can be site specifically targeted to these loci, since DNA damage will accumulate in cancer cells. SpCas9 nickase can be employed to create large numbers of single strand breaks within the genome of proliferating cancer cells by targeting amplified loci. In the context of cancer cells replicating their DNA, these nicks are turned into double strand breaks, which if present in large numbers can lead to cell death. This proof-of-concept project is designed to evaluate the feasibility of generating selective toxicity in cancer cells using Cas9 nickase.