NR ANXL
AU Daude,N.; Marella,M.; Chabry,J.
TI Specific inhibition of pathological prion protein accumulation by small interfering RNAs
QU Journal of Cell Science 2003 Jul 1; 116(13): 2775-9
PT journal article
AB Development of transmissible spongiform encephalopathies (TSEs) pathogenesis requires the presence of both the normal host prion protein (PrP-sen) and the abnormal pathological proteinase-K resistant isoform (PrPres). PrPres forms highly insoluble aggregates, with self-perpetuating properties, by binding and converting PrP-sen molecules into a likeness of themselves. In the present report, we show that small interfering RNA (siRNA) duplexes trigger specific Prnp gene silencing in scrapie-infected neuroblastoma cells. A non-passaged, scrapie-infected culture transfected with siRNA duplexes is depleted of PrP-sen and rapidly loses its PrPres content. The use of different murine-adapted scrapie strains and host cells did not influence the siRNA-induced gene silencing efficiency. More than 80% of transfected cells were positive for the presence of fluorescein-labeled siRNA duplexes. No cytotoxicity associated with the use of siRNA was observed during the time course of these experiments. Despite a transient abrogation of PrPres accumulation, our results suggest that the use of siRNA may provide a new and promising therapeutic approach against prion diseases.
IN Mit kurzen RNA-Strängen schalteten die Autoren in Kulturen Scrapie-infizierter Neuroblastomzellen ohne erkennbare Zytotoxizität die Expression des normalen Prionproteingens aus und erreichten damit sogar ein vorübergehendes Verschwinden des PrPsc.
MH Animals; Cell Line, Tumor; Fluorescein; Gene Silencing/drug effects/*physiology; Mice; PrPc Proteins/genetics/metabolism; PrPsc Proteins/*biosynthesis/genetics; Prion Diseases/genetics/*metabolism/therapy; RNA Interference/*physiology; RNA, Small Interfering/*genetics/pharmacology; Scrapie/genetics/metabolism/therapy; Support, Non-U.S. Gov't; Transfection/methods/trends
AD Institut de Pharmacologie Moleculaire et Cellulaire, Unite Mixte de Recherche 6097, Centre National de la Recherche Scientifique. 660, route des lucioles, 06560 Valbonne, France.
SP englisch
PO England