Sequence- and target-independent angiogenesis suppression by siRNA via TLR3 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-04

AUTHORS

Mark E. Kleinman, Kiyoshi Yamada, Atsunobu Takeda, Vasu Chandrasekaran, Miho Nozaki, Judit Z. Baffi, Romulo J. C. Albuquerque, Satoshi Yamasaki, Masahiro Itaya, Yuzhen Pan, Binoy Appukuttan, Daniel Gibbs, Zhenglin Yang, Katalin Karikó, Balamurali K. Ambati, Traci A. Wilgus, Luisa A. DiPietro, Eiji Sakurai, Kang Zhang, Justine R. Smith, Ethan W. Taylor, Jayakrishna Ambati

ABSTRACT

Clinical trials of small interfering RNA (siRNA) targeting vascular endothelial growth factor-A (VEGFA) or its receptor VEGFR1 (also called FLT1), in patients with blinding choroidal neovascularization (CNV) from age-related macular degeneration, are premised on gene silencing by means of intracellular RNA interference (RNAi). We show instead that CNV inhibition is a siRNA-class effect: 21-nucleotide or longer siRNAs targeting non-mammalian genes, non-expressed genes, non-genomic sequences, pro- and anti-angiogenic genes, and RNAi-incompetent siRNAs all suppressed CNV in mice comparably to siRNAs targeting Vegfa or Vegfr1 without off-target RNAi or interferon-alpha/beta activation. Non-targeted (against non-mammalian genes) and targeted (against Vegfa or Vegfr1) siRNA suppressed CNV via cell-surface toll-like receptor 3 (TLR3), its adaptor TRIF, and induction of interferon-gamma and interleukin-12. Non-targeted siRNA suppressed dermal neovascularization in mice as effectively as Vegfa siRNA. siRNA-induced inhibition of neovascularization required a minimum length of 21 nucleotides, a bridging necessity in a modelled 2:1 TLR3-RNA complex. Choroidal endothelial cells from people expressing the TLR3 coding variant 412FF were refractory to extracellular siRNA-induced cytotoxicity, facilitating individualized pharmacogenetic therapy. Multiple human endothelial cell types expressed surface TLR3, indicating that generic siRNAs might treat angiogenic disorders that affect 8% of the world's population, and that siRNAs might induce unanticipated vascular or immune effects. More... »

PAGES

591

References to SciGraph publications

  • 2006-08. The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing in NATURE CELL BIOLOGY
  • 2004-11. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs in NATURE
  • 2002-02. Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway in NATURE IMMUNOLOGY
  • 2006-02. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1 in GENE THERAPY
  • 2007-01. Illuminating the silence: understanding the structure and function of small RNAs in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2007-06. Interfering with disease: a progress report on siRNA-based therapeutics in NATURE REVIEWS DRUG DISCOVERY
  • 2004-03. Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase in NATURE BIOTECHNOLOGY
  • 2005-06. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors in NATURE BIOTECHNOLOGY
  • 2005-04. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA in NATURE BIOTECHNOLOGY
  • 2003-08. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling in NATURE
  • 2004-12. Lack of interferon response in animals to naked siRNAs in NATURE BIOTECHNOLOGY
  • 2005-03. Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7 in NATURE MEDICINE
  • 2007-01. RNA learns from antisense in NATURE CHEMICAL BIOLOGY
  • 2006-05. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses in NATURE
  • 2004-07. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses in NATURE IMMUNOLOGY
  • 2001-10. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 in NATURE
  • 2006-03. 3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets in NATURE METHODS
  • 2003-09. Activation of the interferon system by short-interfering RNAs in NATURE CELL BIOLOGY
  • 2006-09. Toll-like receptors as molecular switches in NATURE REVIEWS IMMUNOLOGY
  • 2003-06. Expression profiling reveals off-target gene regulation by RNAi in NATURE BIOTECHNOLOGY
  • 2007-10. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs in NATURE BIOTECHNOLOGY
  • Journal

    TITLE

    Nature

    ISSUE

    7187

    VOLUME

    452

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature06765

    DOI

    http://dx.doi.org/10.1038/nature06765

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1030701442

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18368052


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