Single AAV-mediated mutation replacement genome editing in limited number of photoreceptors restores vision in mice.

ABSTRACT: Supplementing wildtype copies of functionally defective genes with adeno-associated virus (AAV) is a strategy being explored clinically for various retinal dystrophies. However, the low cargo limit of this vector allows its use in only a fraction of patients with mutations in relatively small pathogenic genes. To overcome this issue, we developed a single AAV platform that allows local replacement of a mutated sequence with its wildtype counterpart, based on combined CRISPR-Cas9 and micro-homology-mediated end-joining (MMEJ). In blind mice, the mutation replacement rescued approximately 10% of photoreceptors, resulting in an improvement in light sensitivity and an increase in visual acuity. These effects were comparable to restoration mediated by gene supplementation, which targets a great

SUBMITTER: Nishiguchi KM 

PROVIDER: S-EPMC6981188 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature