Modulation of Splicing by Single-Stranded Silencing RNAs
Publication: nucleic acid therapeutics
Volume 25, Issue Number 3
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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Copyright
Copyright 2015, Mary Ann Liebert, Inc.
History
Published in print: June 2015
Published online: 19 May 2015
Published ahead of print: 10 March 2015
Accepted: 2 February 2015
Received: 11 December 2014
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Author Disclosure Statement
T.P. Prakash is an employee of ISIS Pharmaceutical.
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