Publication: Human Gene Therapy. 26: 114-126.
Published Date: February 2015
Provided proof-of-principle for precision genome editing in Fanconi anemia (FA), a DNA repair-deficient human disorder, using CRISPR/Cas9.
Because patients with FA have a premalignant phenotype, the need for safe and effective genome modification is great. Using FA patient-derived, transformed fibroblasts, the authors examined the gene-correction ability of nuclease and nickase versions of Cas9 paired with a mutation-proximal guide RNA of the FANCC gene and found the nickase to be more efficient. Additionally, in an analysis of off-target effects in coding regions sharing homology with the FANCC target site, the authors found no observable off-target activity. Overall, the authors provide support for a favorable safety profile and application of genome editing for human genetic disorders using CRISPR/Cas9.