Background

Recent advances in targeted genome editing have transformed biomedical research. With the advent of the CRISPR/Cas9 system, genome editing has become faster, cheaper, and more accurate, and is now an invaluable tool for researchers in the biological sciences. Although this technology has been revolutionary for the research community and holds great potential for gene therapy, it is not an efficient tool for the targeted integration of transgenes in non-dividing cells. Currently, site-specific transgene integration using CRISPR/Cas9 exploits the homology-directed repair (HDR) pathway, which is inefficient in primary cell types and only functions in actively dividing cells. This limits the utility of CRISPR/Cas9 and other engineered nucleases in non-dividing cells, which are the major constituents of adult tissues.