Inhibition of PrPSc formation by lentiviral gene transfer of PrP containing dominant negative mutations
- 1 November 2004
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 117 (23) , 5591-5597
- https://doi.org/10.1242/jcs.01484
Abstract
Currently, there is no treatment to cure transmissible spongiform encephalopathies. By taking advantage of the `prion-resistant9 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.Keywords
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