In Vivo Screening of Chemically Modified RNA duplexes for their Ability to Induce Innate Immune Responses

Brian Dall Schyth, Jesper Bertram Bramsen, Jørgen Kjems, Jesper Wengel, Niels Lorenzen

    Research output: Contribution to conferencePosterResearchpeer-review

    Abstract

    Due to their sequence specific gene targeting activity siRNAs are regarded as promising active compounds in gene medicine. But one serious problem with delivering siRNAs as treatment is the now well-established non-specific activities of some RNA duplexes. Cellular reactions towards double stranded RNAs include the 2´-5´ oligoadenylate synthetase system, the protein kinase R, RIG-I and Toll-like receptor activated pathways all resulting in antiviral defence mechanism. We have previously shown that antiviral innate immune reactions against double stranded RNAs could be detected in vivo as partial protection against a fish pathogenic virus. This protection corresponded with an interferon response in the fish. Here we use this fish model to screen siRNAs containing various chemical modifications of the RNA backbone for their antiviral activity, the overall aim being identification of an siRNA form with minimal immunostimulatory effects.
    Original languageEnglish
    Publication date2009
    Publication statusPublished - 2009
    Event4th International Conference RNAi2009 : ncRNA: Bridging Biology and Therapy - St. Anne´s College, Oxford, England, UK
    Duration: 1 Jan 2009 → …

    Conference

    Conference4th International Conference RNAi2009 : ncRNA: Bridging Biology and Therapy
    CitySt. Anne´s College, Oxford, England, UK
    Period01/01/2009 → …

    Keywords

    • siRNA

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