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Lipopeptide Delivery of siRNA to the Central Nervous System

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Nanotechnology for Nucleic Acid Delivery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1943))

Abstract

RNA interference is a relatively new tool used to silence specific genes in diverse biological systems. The development of this promising new technique for research and therapeutic use in studying and treating neurological diseases has been hampered by the lack of an efficient way to deliver siRNA transvascularly across the blood-brain barrier (BBB) to the central nervous system (CNS). Here we describe the generation of three different liposomal siRNA delivery vehicles to the CNS using the thin film hydration method. Utilizing cationic or anionic liposomes protects the siRNA from serum nucleases and proteases en route. To deliver the siRNA specifically to the CNS, the liposomes are complexed to a peptide that acts as a neuronal address by binding to nicotinic acetylcholine receptors (nAchRs). When injected intravenously, these liposome–siRNA–peptide complexes (LSPCs) or peptide addressed liposome encapsulated therapeutic siRNA (PALETS) resist serum degradation, effectively cross the BBB and deliver siRNA to AchR-expressing cells to suppress protein expression in the CNS.

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Author information

Authors and Affiliations

  1. Department of Microbiology, Immunology and Pathology, Prion Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA

    Mark D. Zabel, Luke Mollnow & Heather Bender

Authors
  1. Mark D. Zabel
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  2. Luke Mollnow
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  3. Heather Bender
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Corresponding author

Correspondence to Mark D. Zabel .

Editor information

Editors and Affiliations

  1. Laboratory of MacroMolecular Cancer Therapeutics (MMCT), Department of Pharmaceutical Chemistry, Center of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria

    Manfred Ogris

  2. Laboratory of MacroMolecular Cancer Therapeutics (MMCT), Department of Pharmaceutical Chemistry, Center of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria

    Haider Sami

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Zabel, M.D., Mollnow, L., Bender, H. (2019). Lipopeptide Delivery of siRNA to the Central Nervous System. In: Ogris, M., Sami, H. (eds) Nanotechnology for Nucleic Acid Delivery. Methods in Molecular Biology, vol 1943. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9092-4_26

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  • DOI: https://doi.org/10.1007/978-1-4939-9092-4_26

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9091-7

  • Online ISBN: 978-1-4939-9092-4

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