Modulation of Splicing by Single-Stranded Silencing RNAs

Jing Liu, Jiaxin Hu, Jessica A. Hicks, Thazha P. Prakash, David R. Corey

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)113-120
Number of pages8
JournalNucleic Acid Therapeutics
Volume25
Issue number3
DOIs
StatePublished - Jun 1 2015

Fingerprint

RNA Interference
Modulation
RNA
Oligonucleotides
Protein Isoforms
Gene expression
RNA Splicing
Gene Expression
Dystrophin
RNA Splice Sites
Cell Nucleus
Seeds
Patents and inventions
Machinery
Seed
Therapeutics
Cells

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Biochemistry
  • Drug Discovery

Cite this

Modulation of Splicing by Single-Stranded Silencing RNAs. / Liu, Jing; Hu, Jiaxin; Hicks, Jessica A.; Prakash, Thazha P.; Corey, David R.

In: Nucleic Acid Therapeutics, Vol. 25, No. 3, 01.06.2015, p. 113-120.

Research output: Contribution to journalArticle

Liu, Jing ; Hu, Jiaxin ; Hicks, Jessica A. ; Prakash, Thazha P. ; Corey, David R. / Modulation of Splicing by Single-Stranded Silencing RNAs. In: Nucleic Acid Therapeutics. 2015 ; Vol. 25, No. 3. pp. 113-120.
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