Trinucleotide Repeat-Targeting dCas9 as a Therapeutic Strategy for Fuchs' Endothelial Corneal Dystrophy.

ABSTRACT:

Purpose

Fuchs' endothelial corneal dystrophy (FECD) is the leading indication for corneal transplantation. Seventy percent of cases are caused by an intronic CTG triplet repeat expansion in the TCF4 gene that results in accumulation of pathogenic expanded CUG repeat RNA (CUG^exp) as nuclear foci in corneal endothelium. A catalytically dead Cas9 (dCas9) can serve as an effective guide to target genomic DNA or RNA transcripts. Here, we examined the utility of the clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9 system to effectively target and reduce CUG^exp.

Methods

We delivered dCas9 and repeat-targeting single guide RNA (sgRNA) expression plasmids to patient-derived endothelial cells using lipofection or lentiviral transduc

SUBMITTER: Rong Z 

PROVIDER: S-EPMC7463221 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature