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

EA pdf-Datei

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