Precise therapeutic gene correction by a simple nuclease-induced double-stranded break.

ABSTRACT: Current programmable nuclease-based methods (for example, CRISPR-Cas9) for the precise correction of a disease-causing genetic mutation harness the homology-directed repair pathway. However, this repair process requires the co-delivery of an exogenous DNA donor to recode the sequence and can be inefficient in many cell types. Here we show that disease-causing frameshift mutations that result from microduplications can be efficiently reverted to the wild-type sequence simply by generating a DNA double-stranded break near the centre of the duplication. We demonstrate this in patient-derived cell lines for two diseases: limb-girdle muscular dystrophy type 2G (LGMD2G)¹ and Hermansky-Pudlak syndrome type 1 (HPS1)². Clonal analysis of inducible pluripotent stem (iPS) cells

SUBMITTER: Iyer S 

PROVIDER: S-EPMC6483862 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature