Inhibition of PrPSc formation by lentiviral gene transfer of PrP containing dominant negative mutations.
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.
Crozet
Carole
C
Laboratoire de Biologie des Encéphalopathies Spongiformes, CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier CEDEX 5, France.
Lin
Yea-Lih
YL
Mettling
Clément
C
Mourton-Gilles
Chantal
C
Corbeau
Pierre
P
Lehmann
Sylvain
S
Perrier
Véronique
V
D000682:Amyloid / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D016089:Immunodeficiency Virus, Feline / Q000235:genetics; D016086:Lentivirus / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D018621:PrPC Proteins / Q000235:genetics; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics; D014161:Transduction, Genetic / Q000379:methods; D014759:Viral Envelope Proteins / Q000235:genetics
D000682:Amyloid; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D018621:PrPC Proteins; D018620:PrPSc Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors; D014759:Viral Envelope Proteins