Designing highly active siRNAs for therapeutic applications

S. Patrick Walton, Ming Wu, Joseph A. Gredell, Christina Chan

Research output: Contribution to journalArticle

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Abstract

The discovery of RNA interference (RNAi) generated considerable interest in developing short interfering RNAs (siRNAs) for understanding basic biology and as the active agents in a new variety of therapeutics. Early studies showed that selecting an active siRNA was not as straightforward as simply picking a sequence on the target mRNA and synthesizing the siRNA complementary to that sequence. As interest in applying RNAi has increased, the methods for identifying active siRNA sequences have evolved from focusing on the simplicity of synthesis and purification, to identifying preferred target sequences and secondary structures, to predicting the thermodynamic stability of the siRNA. As more specific details of the RNAi mechanism have been defined, these have been incorporated into more complex siRNA selection algorithms, increasing the reliability of selecting active siRNAs against a single target. Ultimately, design of the best siRNA therapeutics will require design of the siRNA itself, in addition to design of the vehicle and other components necessary for it to function in vivo. In this minireview, we summarize the evolution of siRNA selection techniques with a particular focus on one issue of current importance to the field, how best to identify those siRNA sequences likely to have high activity. Approaches to designing active siRNAs through chemical and structural modifications will also be highlighted. As the understanding of how to control the activity and specificity of siRNAs improves, the potential utility of siRNAs as human therapeutics will concomitantly grow.

LanguageEnglish (US)
Pages4806-4813
Number of pages8
JournalFEBS Journal
Volume277
Issue number23
DOIs
StatePublished - Dec 2010

Profile

Small Interfering RNA
Therapeutics
RNA Interference
RNA
Thermodynamics
Purification
Thermodynamic stability

Keywords

  • Asymmetry
  • Chemical modifications
  • Design
  • RNAi
  • Selection
  • SiRNA
  • Structural modifications
  • Terminal nucleotides
  • Therapeutics
  • Thermodynamics

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Designing highly active siRNAs for therapeutic applications. / Patrick Walton, S.; Wu, Ming; Gredell, Joseph A.; Chan, Christina.

In: FEBS Journal, Vol. 277, No. 23, 12.2010, p. 4806-4813.

Research output: Contribution to journalArticle

Patrick Walton, S. ; Wu, Ming ; Gredell, Joseph A. ; Chan, Christina. / Designing highly active siRNAs for therapeutic applications. In: FEBS Journal. 2010 ; Vol. 277, No. 23. pp. 4806-4813
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