Designing highly active siRNAs for therapeutic applications

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

    Research output: Contribution to journalArticle

    • 46 Citations

    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.

    Original languageEnglish (US)
    Pages (from-to)4806-4813
    Number of pages8
    JournalFEBS Journal
    Volume277
    Issue number23
    DOIs
    StatePublished - Dec 2010

    Profile

    Small Interfering RNA
    RNA Interference
    Thermodynamics
    Messenger RNA
    Inborn Errors Amino Acid Metabolism
    Alcuronium
    Clodronic Acid
    Cerebellar Ataxia
    Blood Flow Velocity
    Airway Obstruction
    Autistic Disorder
    Analgesia
    Purification

    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, Vol. 277, No. 23, 12.2010, p. 4806-4813.

    Research output: Contribution to journalArticle

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