Antisense suppression of the nonsense mediated decay factor Upf3b as a potential treatment for diseases caused by nonsense mutations.

ABSTRACT:

Background

About 11% of all human genetic diseases are caused by nonsense mutations that generate premature translation termination codons (PTCs) in messenger RNAs (mRNA). PTCs not only lead to the production of truncated proteins, but also often result in  decreased mRNA abundance due to  nonsense-mediated mRNA decay (NMD). Although pharmacological inhibition of NMD could be an attractive therapeutic approach for the treatment of diseases caused by nonsense mutations, NMD also regulates the expression of 10-20% of the normal transcriptome.

Results

Here, we investigate whether NMD can be inhibited to stabilize mutant mRNAs, which may subsequently produce functional proteins, without having a major impact on the normal transcriptome. We develop antisense oligonucleotides (ASO

SUBMITTER: Huang L 

PROVIDER: S-EPMC5769327 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature