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         headline:A combinatorial library of lipid-like materials for delivery of RNAi therapeutics
         description:The safe and effective delivery of RNA interference (RNAi) therapeutics remains an important challenge for clinical development. The diversity of current delivery materials remains limited, in part because of their slow, multi-step syntheses. Here we describe a new class of lipid-like delivery molecules, termed lipidoids, as delivery agents for RNAi therapeutics. Chemical methods were developed to allow the rapid synthesis of a large library of over 1,200 structurally diverse lipidoids. From this library, we identified lipidoids that facilitate high levels of specific silencing of endogenous gene transcripts when formulated with either double-stranded small interfering RNA (siRNA) or single-stranded antisense 2′-O-methyl (2′-OMe) oligoribonucleotides targeting microRNA (miRNA). The safety and efficacy of lipidoids were evaluated in three animal models: mice, rats and nonhuman primates. The studies reported here suggest that these materials may have broad utility for both local and systemic delivery of RNA therapeutics.
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      headline:A combinatorial library of lipid-like materials for delivery of RNAi therapeutics
      description:The safe and effective delivery of RNA interference (RNAi) therapeutics remains an important challenge for clinical development. The diversity of current delivery materials remains limited, in part because of their slow, multi-step syntheses. Here we describe a new class of lipid-like delivery molecules, termed lipidoids, as delivery agents for RNAi therapeutics. Chemical methods were developed to allow the rapid synthesis of a large library of over 1,200 structurally diverse lipidoids. From this library, we identified lipidoids that facilitate high levels of specific silencing of endogenous gene transcripts when formulated with either double-stranded small interfering RNA (siRNA) or single-stranded antisense 2′-O-methyl (2′-OMe) oligoribonucleotides targeting microRNA (miRNA). The safety and efficacy of lipidoids were evaluated in three animal models: mice, rats and nonhuman primates. The studies reported here suggest that these materials may have broad utility for both local and systemic delivery of RNA therapeutics.
      datePublished:2008-04-27T00:00:00Z
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         Bioinformatics
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            name:David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
            address:
               name:David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, USA
               type:PostalAddress
            type:Organization
            name:Massachusetts Institute of Technology
            address:
               name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
               type:PostalAddress
            type:Organization
            name:Massachusetts Institute of Technology
            address:
               name:Department of Chemistry, Massachusetts Institute of Technology, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Daniel G Anderson
      affiliation:
            name:David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
            address:
               name:David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Organic Chemistry, University of Geneva, Switzerland
      name:Department of Chemistry, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Europe AG, Kulmbach, Germany
      name:Present addresses: Roche Kulmbach GmbH, Fritz-Hornschuch-Str. 9, 95326 Kulmbach, Germany (R.C., M.J. and H.-P.V.) and Regulus Therapeutics, 1896 Rutherford Road, Carlsbad, California 92008, USA (J.S.).,
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Europe AG, Kulmbach, Germany
      name:Present addresses: Roche Kulmbach GmbH, Fritz-Hornschuch-Str. 9, 95326 Kulmbach, Germany (R.C., M.J. and H.-P.V.) and Regulus Therapeutics, 1896 Rutherford Road, Carlsbad, California 92008, USA (J.S.).,
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Europe AG, Kulmbach, Germany
      name:Present addresses: Roche Kulmbach GmbH, Fritz-Hornschuch-Str. 9, 95326 Kulmbach, Germany (R.C., M.J. and H.-P.V.) and Regulus Therapeutics, 1896 Rutherford Road, Carlsbad, California 92008, USA (J.S.).,
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:Alnylam Europe AG, Kulmbach, Germany
      name:Present addresses: Roche Kulmbach GmbH, Fritz-Hornschuch-Str. 9, 95326 Kulmbach, Germany (R.C., M.J. and H.-P.V.) and Regulus Therapeutics, 1896 Rutherford Road, Carlsbad, California 92008, USA (J.S.).,
      name:Alnylam Pharmaceuticals, Inc., Cambridge, USA
      name:David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Chemistry, Massachusetts Institute of Technology, Cambridge, USA
      name:David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, USA
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