Mapping the Cellular Determinants of Genome Editing in Human Cells

Efforts to repurpose CRISPR-Cas systems have produced a suite of genome editing tools, including programmable nucleases, base editors, and prime editors. These tools have greatly enabled the study of genomes and gene function, and their advancement to therapeutic development has demonstrated promise for addressing a host of unmet medical needs. Our understanding of how endogenous cellular processes influence the activity of these tools, however, lags far behind their application and, due to the rapid pace of technology development, behind efforts to build new approaches. Our work focuses on identifying cellular determinants of genome editing tools to better understand how they work. Our results provide key insights into how those tools interact with the cellular environment and suggest general strategies for improvement.