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Cited by 85RNA Interference and Gene DeliveryPrion Diseases and Protein MisfoldingNanoparticle-Based Drug Delivery

Liposome-siRNA-Peptide Complexes Cross the Blood-Brain Barrier and Significantly Decrease PrPC on Neuronal Cells and PrPRES in Infected Cell Cultures

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Pulford, Bruce, Reim, Natalia, Bell, Aimee, Veatch, Jessica, Forster, Genevieve, Bender, Heather, Meyerett, Crystal, Hafeman, Scott +9 more·2010·PLoS ONE
DOI 10.1371/journal.pone.0011085PMC PMC2885418
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Abstract

BACKGROUND: Recent advances toward an effective therapy for prion diseases employ RNA interference to suppress PrP(C) expression and subsequent prion neuropathology, exploiting the phenomenon that disease severity and progression correlate with host PrP(C) expression levels. However, delivery of lentivirus encoding PrP shRNA has demonstrated only modest efficacy in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a new siRNA delivery system incorporating a small peptide that binds siRNA and acetylcholine receptors (AchRs), acting as a molecular messenger for delivery to neurons, and cationic liposomes that protect siRNA-peptide complexes from serum degradation. CONCLUSIONS/SIGNIFICANCE: Liposome-siRNA-peptide complexes (LSPCs) delivered PrP siRNA specifically to AchR-expressing cells, suppressed PrP(C) expression and eliminated PrP(RES) formation in vitro. LSPCs injected intravenously into mice resisted serum degradation and delivered PrP siRNA throughout the brain to AchR and PrP(C)-expressing neurons. These data promote LSPCs as effective vehicles for delivery of PrP and other siRNAs specifically to neurons to treat prion and other neuropathological diseases.

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Authors
Pulford, B., Reim, N., Bell, A., Veatch, J., Forster, G., Bender, H., Meyerett, C., Hafeman, S., Michel, B., Johnson, T., Wyckoff, A. C., Miele, G., Julius, C., Kranich, J., Schenkel, A., Dow, S., & Zabel, M. D.
Affiliations
  • Colorado State University (US)
  • Garvan Institute of Medical Research (AU)
Corresponding author
Zabel, Mark D.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-06-14
Volume
5
Issue
6
Pages
e11085
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0011085
PMC
PMC2885418
OpenAlex
W2012913690
Cited by
85
References
72
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 6 · 2012: 12
FWCI
3.52
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Colorado State University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
prion disease, siRNA delivery, cationic liposomes, acetylcholine receptor, blood-brain barrier, RNA interference, neuronal targeting, intravenous injection, serum stability, neurodegenerative disease treatment
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Blood-Brain Barrier, Cell Line, Cells, Cultured, Liposomes, Molecular Sequence Data, Neurons, Prions, RNA, Small Interfering, Mice

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