Maximizing lentiviral vector gene transfer in the CNS.

Details

Serval ID
serval:BIB_D51007012CC2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Maximizing lentiviral vector gene transfer in the CNS.
Journal
Gene therapy
Author(s)
Humbel M., Ramosaj M., Zimmer V., Regio S., Aeby L., Moser S., Boizot A., Sipion M., Rey M., Déglon N.
ISSN
1476-5462 (Electronic)
ISSN-L
0969-7128
Publication state
Published
Issued date
06/07/2020
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Gene transfer is a widely developed technique for studying and treating genetic diseases. However, the development of therapeutic strategies is challenging, due to the cellular and functional complexity of the central nervous system (CNS), its large size and restricted access. We explored two parameters for improving gene transfer efficacy and capacity for the selective targeting of subpopulations of cells with lentiviral vectors (LVs). We first developed a second-generation LV specifically targeting astrocytes for the efficient expression or silencing of genes of interest, and to better study the importance of cell subpopulations in neurological disorders. We then made use of the retrograde transport properties of a chimeric envelope to target brain circuits affected in CNS diseases and achieve a broad distribution. The combination of retrograde transport and specific tropism displayed by this LV provides opportunities for delivering therapeutic genes to specific cell populations and ensuring high levels of transduction in interconnected brain areas following local administration. This new LV and delivery strategy should be of greater therapeutic benefit and opens up new possibilities for the preclinical development of gene therapy for neurodegenerative diseases.
Pubmed
Open Access
Yes
Create date
13/07/2020 12:30
Last modification date
17/07/2020 6:26
Usage data