Antisense oligonucleotide-directed inhibition of nonsense-mediated mRNA decay.

Nomakuchi, Tomoki T; Rigo, Frank; Aznarez, Isabel; Krainer, Adrian R · Nat Biotechnol · 2016

basic_science · Level V

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Abstract

Nonsense-mediated mRNA decay (NMD) is a cellular quality-control mechanism that is thought to exacerbate the phenotype of certain pathogenic nonsense mutations by preventing the expression of semi-functional proteins. NMD also limits the efficacy of read-through compound (RTC)-based therapies. Here, we report a gene-specific method of NMD inhibition using antisense oligonucleotides (ASOs) and combine this approach with an RTC to effectively restore the expression of full-length protein from a nonsense-mutant allele.

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