In two papers published in Cell Stem Cell in 2014, we demonstrated the genomic consequences of CRISPR/Cas9 genome editing technology, both at the targeted site of alteration and through genome-wide analyses to identify unintended mutagenesis through off-target effects. In both studies, our analyses suggest that the off-target effects of CRISPR/Cas9 are minimal, and that the high efficiency of on-target alterations could hold promise for therapeutic development. Both studies were collaborations with investigators outside of the CHGR, and in the latter study, led by Chad Cowan and Derek Rossi, we demonstrated efficient ablation of CCR5, a receptor required for HIV receptor, in human HSCs. This study suggests that future efforts to deliver CCR5 deficient HSCs could promote HIV resistance in the immune system.
Veres A, Ding Q, Bridget GS, Collins R, Ragavendran A, Brand H, Erdin S, Talkowski ME & Musunuru K. Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones assessed by whole-genome sequencing. Cell Stem Cell. 2014 Jul 3;15(1):27-30.
Mandal PK, Ferreira LMR, Collins R, Meissner TB, Boutwell CL, Friesen M, Garrison BS, Stortchevoi A, Bryder D, Musunuru K, Brand H, Allen TM, Talkowski ME, Rossi DJ*, Cowan, CA*. Efficient ablation of clinically relevant genes in human hematopoietic cells using CRISPR/Cas9. Cell Stem Cell. Nov 6;15(5):643-52.