Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA.

ABSTRACT: Ocular gene therapy with recombinant adeno-associated virus (AAV) has shown vector-mediated gene augmentation to be safe and efficacious in the retina in one set of diseases (retinitis pigmentosa and Leber congenital amaurosis (LCA) caused by RPE65 deficiency), with excellent safety profiles to date and potential for efficacy in several additional diseases. However, size constraints imposed by the packaging capacity of the AAV genome restrict application to diseases with coding sequence lengths that are less than 5,000 nt. The most prevalent retinal diseases with monogenic inheritance are caused by mutations in genes that exceed this capacity. Here, we designed a spliceosome mediated pre-mRNA trans-splicing strategy to rescue expression of CEP290, which is associated with Leber congenital

SUBMITTER: Dooley SJ 

PROVIDER: S-EPMC6023944 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature