title: Liposome-siRNA-peptide complexes cross the blood-brain barrier and significantly decrease PrP on neuronal cells and PrP in infected cell cultures.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Microbiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Bruce
authors.initials: B
authors.lastname: Pulford
authors.forename: Natalia
authors.initials: N
authors.lastname: Reim
authors.forename: Aimee
authors.initials: A
authors.lastname: Bell
authors.forename: Jessica
authors.initials: J
authors.lastname: Veatch
authors.forename: Genevieve
authors.initials: G
authors.lastname: Forster
authors.forename: Heather
authors.initials: H
authors.lastname: Bender
authors.forename: Crystal
authors.initials: C
authors.lastname: Meyerett
authors.forename: Scott
authors.initials: S
authors.lastname: Hafeman
authors.forename: Brady
authors.initials: B
authors.lastname: Michel
authors.forename: Theodore
authors.initials: T
authors.lastname: Johnson
authors.forename: A Christy
authors.initials: AC
authors.lastname: Wyckoff
authors.forename: Gino
authors.initials: G
authors.lastname: Miele
authors.forename: Christian
authors.initials: C
authors.lastname: Julius
authors.forename: Jan
authors.initials: J
authors.lastname: Kranich
authors.forename: Alan
authors.initials: A
authors.lastname: Schenkel
authors.forename: Steven
authors.initials: S
authors.lastname: Dow
authors.forename: Mark D
authors.initials: MD
authors.lastname: Zabel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001812:Blood-Brain Barrier; D002460:Cell Line; D002478:Cells, Cultured; D008081:Liposomes; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000493:pharmacokinetics*
chemical_list: D008081:Liposomes; D011328:Prions; D034741:RNA, Small Interfering