Nomakuchi Tomoki T, Rigo Frank, Aznarez Isabel, Krainer Adrian R
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Stony Brook University School of Medicine, Stony Brook, New York, USA.
Nat Biotechnol. 2016 Feb;34(2):164-6. doi: 10.1038/nbt.3427. Epub 2015 Dec 14.
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.
无义介导的mRNA衰变（NMD）是一种细胞质量控制机制，人们认为它通过阻止半功能蛋白的表达来加剧某些致病性无义突变的表型。NMD还限制了基于通读化合物（RTC）疗法的疗效。在此，我们报告了一种使用反义寡核苷酸（ASO）抑制NMD的基因特异性方法，并将这种方法与RTC相结合，以有效地从无义突变等位基因中恢复全长蛋白的表达。
