Designing Ago2-specific siRNA/shRNA to avoid competition with endogenous miRNAs

Hongming Ma, Junli Zhang, Haoquan Wu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Relatively large amounts of transfected siRNA can compete for Ago proteins and thus compromise endogenous miRNA function, potentially leading to toxicities. Here, we show that shRNA can also perturb endogenous miRNA function similarly. More importantly, we also show that the problem can be solved by designing shRNAs in the context of pre-miR-451 structure with completely complementary stem, which significantly improves the Ago2 specificity. This shRNA was shown to be Ago2-specific, and maintain target-silencing ability while avoiding competition with endogenous miRNAs by not competing for Agos 1, 3, and 4. We conclude that modified pre-miR-451 structure provides a general platform to design shRNAs that significantly reduce perturbation of miRNA function.

Original languageEnglish
Article numbere176
Pages (from-to)e176
JournalMolecular Therapy - Nucleic Acids
Volume3
DOIs
StatePublished - Jul 1 2014
Externally publishedYes

Keywords

  • Ago2
  • Dicer
  • MiR-451
  • ShRNA

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