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- Title
Liposome-siRNA-Peptide Complexes Cross the Blood- Brain Barrier and Significantly Decrease PrP<sup>C</sup> on Neuronal Cells and PrP<sup>RES</sup> in Infected Cell Cultures.
- Authors
Pulford, Bruce; Reim, Natalia; Bell, Aimee; Veatch, Jessica; Forster, Genevieve; Bender, Heather; Meyerett, Crystal; Hafeman, Scott; Michel, Brady; Johnson, Theodore; Wyckoff, A. Christy; Miele, Gino; Julius, Christian; Kranich, Jan; Schenkel, Alan; Dow, Steven; Zabel, Mark D.
- Abstract
Background: Recent advances toward an effective therapy for prion diseases employ RNA interference to suppress PrPC expression and subsequent prion neuropathology, exploiting the phenomenon that disease severity and progression correlate with host PrPC 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 PrPC expression and eliminated PrPRES formation in vitro. LSPCs injected intravenously into mice resisted serum degradation and delivered PrP siRNA throughout the brain to AchR and PrPC-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.
- Publication
PLoS ONE, 2010, Vol 5, Issue 6, p1
- ISSN
1932-6203
- Publication type
Academic Journal
- DOI
10.1371/journal.pone.0011085