Modulation of Splicing by Single-Stranded Silencing RNAs

Nucleic Acid Therapeutics
Jing LiuDavid R Corey

Abstract

Single-stranded silencing RNAs (ss-siRNAs) are chemically modified single-stranded oligonucleotides that can function through the cellular RNA interference (RNAi) machinery to modulate gene expression. Because their invention is recent, few studies have appeared describing their use and the potential of ss-siRNAs as a platform for controlling gene expression remains largely unknown. Using oligonucleotides to modulate splicing is an important area for therapeutic development and we tested the hypothesis that ss-siRNAs targeting splice sites might also be capable of directing increased production of therapeutically promising protein isoforms. Here we observe that ss-siRNAs alter splicing of dystrophin. Altered splicing requires a seed sequence complementarity to the target and expression of the RNAi factor argonaute 2. These results demonstrate that ss-siRNAs can be used to modulate splicing, providing another option for therapeutic development programs that aim to increase production of key protein isoforms. Splicing is a classical nuclear process and our data showing that it can be modulated through the action of RNA and RNAi factors offers further evidence that RNAi can take place in mammalian cell nuclei.

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Citations

Nov 28, 2015·Nucleic Acids Research·Roya KalantariDavid R Corey
Apr 29, 2016·Nucleic Acid Therapeutics·Hannah M PendergraffJonathan K Watts
Oct 19, 2016·International Journal of Molecular Sciences·Caterina CatalanottoGiuseppe Zardo
Dec 23, 2016·Nucleic Acid Therapeutics·Jiaxin HuDavid R Corey
Dec 15, 2017·Briefings in Functional Genomics·Xiaoxia MaYijun Meng
Oct 6, 2020·Nucleic Acid Therapeutics·Kenji HagiwaraFumikazu Shinohara

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Datasets Mentioned

BETA
GM03429

Methods Mentioned

BETA
antisense oligonucleotides
transfection
PCR
electrophoresis
antisense oligonucleotide
biopsy

Software Mentioned

ImageJ

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