Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2010 Jun 14;5(6):e11085. doi: 10.1371/journal.pone.0011085.

Liposome-siRNA-peptide complexes cross the blood-brain barrier and significantly decrease PrP on neuronal cells and PrP in infected cell cultures.

Author information

  • 1Department of Microbiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.

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.

PMID:
20559428
[PubMed - indexed for MEDLINE]
PMCID:
PMC2885418
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk