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Inhibiting AIDS in the central nervous system: gene delivery to protect neurons from HIV
Journal article   Peer reviewed

Inhibiting AIDS in the central nervous system: gene delivery to protect neurons from HIV

Pierre Cordelier, Elisabeth Van Bockstaele, Sandra A Calarota and David S Strayer
Molecular therapy, v 7(6), pp 801-810
Jun 2003
PMID: 12788654
url
https://doi.org/10.1016/S1525-0016(03)00093-5View
Published, Version of Record (VoR) Restricted

Abstract

gene therapy neuro-AIDS NT2 cells RevM10 SV40 α1-antitrypsin
Gene therapy to treat primary and secondary CNS diseases, including neuro-AIDS, has not yet been effective. New approaches to delivering therapeutic genes to the central nervous system are therefore required. Recombinant SV40 vectors (rSV40) transduce both dividing and quiescent cells efficiently, and so we tested them for their ability to deliver anti-HIV-1 transgenes to terminally differentiated human NT2-derived neurons (NT2-N). These vectors transduced>95% of immature as well as mature human neurons efficiently, without detectable toxicity and without requiring selection. rSV40 gene delivery was stable to retinoic acid-induced neuronal differentiation. The rSV40 vectors used in these studies, SV(RevM10) and SV(AT), respectively carried the cDNAs for RevM10, a trans-dominant mutant of HIV-1 Rev, and human α1-antitrypsin. As measured by HIV-1 p24 antigen assays and by immunostaining for gp120, NT2-N treated with these vectors strongly resisted challenge with different strains of HIV-1. Protection from HIV replication and HIV-induced cytotoxicity was conferred by SV(AT) and SV(RevM10) and remained constant throughout retinoic acid-induced neuronal differentiation and for the duration of these studies (≥11 weeks). rSV40 transduction of human neurons might therefore be a practicable approach to gene delivery for the treatment of CNS diseases, including neuro-AIDS.

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Web of Science research areas
Biotechnology & Applied Microbiology
Genetics & Heredity
Medicine, Research & Experimental
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