Approaches to Enhance Precise CRISPR/Cas9-Mediated Genome Editing

Christopher E. Denes, Alexander J. Cole, Yagiz Alp Aksoy, Geng Li, G. Gregory Neely, Daniel Hesselson
2021 International Journal of Molecular Sciences  
Modification of the human genome has immense potential for preventing or treating disease. Modern genome editing techniques based on CRISPR/Cas9 show great promise for altering disease-relevant genes. The efficacy of precision editing at CRISPR/Cas9-induced double-strand breaks is dependent on the relative activities of nuclear DNA repair pathways, including the homology-directed repair and error-prone non-homologous end-joining pathways. The competition between multiple DNA repair pathways
more » ... rates mosaic and/or therapeutically undesirable editing outcomes. Importantly, genetic models have validated key DNA repair pathways as druggable targets for increasing editing efficacy. In this review, we highlight approaches that can be used to achieve the desired genome modification, including the latest progress using small molecule modulators and engineered CRISPR/Cas proteins to enhance precision editing.
doi:10.3390/ijms22168571 pmid:34445274 pmcid:PMC8395304 fatcat:rj24utrhb5f5xdrkto2zet3q2a