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

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,...

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Detalles Bibliográficos
Autores principales: Nomakuchi, Tomoki T., Rigo, Frank, Aznarez, Isabel, Krainer, Adrian R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744113/
https://www.ncbi.nlm.nih.gov/pubmed/26655495
http://dx.doi.org/10.1038/nbt.3427
Descripción
Sumario: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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