Allele-specific gene editing prevents deafness in a model of dominant progressive hearing loss.

ABSTRACT: Since most dominant human mutations are single nucleotide substitutions^1,2, we explored gene editing strategies to disrupt dominant mutations efficiently and selectively without affecting wild-type alleles. However, single nucleotide discrimination can be difficult to achieve³ because commonly used endonucleases, such as Streptococcus pyogenes Cas9 (SpCas9), can tolerate up to seven mismatches between guide RNA (gRNA) and target DNA. Furthermore, the protospacer-adjacent motif (PAM) in some Cas9 enzymes can tolerate mismatches with the target DNA^3,4. To circumvent these limitations, we screened 14 Cas9/gRNA combinations for specific and efficient disruption of a nucleotide substitution that causes the dominant progressive hearing loss, DFNA36. As a model fo

SUBMITTER: Gyorgy B 

PROVIDER: S-EPMC6802276 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature