NR AROS
AU Crozet,C.A.; Lin,Y.L.; Mettling,C.; Mourton-Gilles,C.; Corbeau,P.; Lehmann,S.; Perrier,V.
TI Inhibition of PrPsc formation by lentiviral gene transfer of PrP containing dominant negative mutations
QU Journal of Cell Science 2004 Nov 1; 117(23): 5591-7
PT journal article
AB Currently, there is no treatment to cure transmissible spongiform encephalopathies. By taking advantage of the 'prion-resistant' polymorphisms Q171R and E219K that naturally exist in sheep and humans, respectively, we have evaluated a therapeutic approach of lentiviral gene transfer. Here, we show that VSV-G (vesicular stomatitis virus G glycoprotein) pseudotyped FIV-(feline immunodeficiency virus) derived vectors carrying the mouse Prnp gene in which these mutations have been inserted, are able to inhibit prion replication in chronically prion-infected cells. Because lentiviral tools are able to transduce post-mitotic cells such as neurons or cells of the lymphoreticular system, this result might help the development of gene- or cell-therapy approaches to prion disease.
MH Amyloid/genetics; Animals; Brain/metabolism/pathology/physiopathology; Cell Line, Tumor; Cells, Cultured; Gene Therapy/*methods; Genetic Vectors/*genetics; Immunodeficiency Virus, Feline/genetics; Lentivirus/*genetics; Membrane Glycoproteins/genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation/genetics; Polymorphism, Genetic/genetics; PrPc Proteins/genetics; PrPsc Proteins/*antagonists & inhibitors/*genetics/metabolism; Prion Diseases/genetics/metabolism/*therapy; Protein Precursors/genetics; Transduction, Genetic/methods; Viral Envelope Proteins/genetics
AD Carole Crozet, Laboratoire de Biologie des Encephalopathies Spongiformes, CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier CEDEX 5, France.
SP englisch
PO England