Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression.

ABSTRACT: While most monogenic diseases are caused by loss or reduction of protein function, the need for technologies that can selectively increase levels of protein in native tissues remains. Here we demonstrate that antisense-mediated modulation of pre-mRNA splicing can increase endogenous expression of full-length protein by preventing naturally occurring non-productive alternative splicing and promoting generation of productive mRNA. Bioinformatics analysis of RNA sequencing data identifies non-productive splicing events in 7,757 protein-coding human genes, of which 1,246 are disease-associated. Antisense oligonucleotides targeting multiple types of non-productive splicing events lead to increases in productive mRNA and protein in a dose-dependent manner in vitro. Moreover, intracerebroventricu

SUBMITTER: Lim KH 

PROVIDER: S-EPMC7347940 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature