Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates
-
- Yizhou Dong
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Kevin T. Love
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- J. Robert Dorkin
- Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Sasilada Sirirungruang
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Yunlong Zhang
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Delai Chen
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Roman L. Bogorad
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Hao Yin
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Yi Chen
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Arturo J. Vegas
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Christopher A. Alabi
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Gaurav Sahay
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Karsten T. Olejnik
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Weiheng Wang
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Avi Schroeder
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Abigail K. R. Lytton-Jean
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Daniel J. Siegwart
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Akin Akinc
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Carmen Barnes
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Scott A. Barros
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Mary Carioto
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Kevin Fitzgerald
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Julia Hettinger
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Varun Kumar
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Tatiana I. Novobrantseva
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- June Qin
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- William Querbes
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Victor Koteliansky
- Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142; and
-
- Robert Langer
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
-
- Daniel G. Anderson
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
説明
<jats:title>Significance</jats:title> <jats:p> The safe, selective, and efficient delivery of siRNA is a key challenge to the broad application of siRNA therapeutics in humans. Motivated by the structure of lipoproteins, we developed lipopeptide nanomaterials for siRNA delivery. In vivo in mice, siRNA–lipopeptide particles provide the most potent delivery to hepatocytes (ED <jats:sub>50</jats:sub> ∼ 0.002 mg/kg for FVII silencing), with the highest selectivity of delivery to hepatocytes over nontarget cell types (orders of magnitude), yet reported. These materials also show efficacy in nonhuman primates. </jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 111 (11), 3955-3960, 2014-02-10
Proceedings of the National Academy of Sciences