| Autor: |
Bruce Pulford, Natalia Reim, Aimee Bell, Jessica Veatch, Genevieve Forster, Heather Bender, Crystal Meyerett, Scott Hafeman, Brady Michel, Theodore Johnson, A Christy Wyckoff, Gino Miele, Christian Julius, Jan Kranich, Alan Schenkel, Steven Dow, Mark D Zabel |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 5, Iss 6, p e11085 (2010) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0011085 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
