AIDSWEEKLY Plus; Monday, August 4, 2003
Staff Medical Writers

"Gene therapy to treat primary and secondary CNS diseases, including neuro-AIDS, has not yet been effective," researchers in the United States noted. "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 were tested by P. Cordelier and coauthors at Jefferson Medical College in Philadelphia "for their ability to deliver anti-HIV-1 transgenes to terminally differentiated human NT2-derived neurons (NT2-N)."

"These vectors transduced more than 95% of immature as well as mature human neurons efficiently, without detectable toxicity and without requiring selection," they wrote in the journal Molecular Therapy. In addition, "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 alpha1-antitrypsin," according to the report. "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 (greater than or equal to one week)," study data showed.

The researchers concluded that "rSV40 transduction of human neurons might therefore be a practicable approach to gene delivery for the treatment of CNS diseases, including neuro-AIDS."

Cordelier and colleagues published their study in Molecular Therapy (Inhibiting AIDS in the central nervous system: Gene delivery to protect neurons from HIV. Mol Ther. 2003 Jun;7(6):801-10.

For additional information, contact D.S. Strayer, Jefferson Medical College, Department of Pathology, 1020 Locust St., Room 251, Philadelphia, PA 19107, USA.

Publisher contact information for the journal Molecular Therapy is: Academic Press Inc. Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495, USA.

The information in this article comes under the major subject areas of AIDS and HIV, Biotechnology, Gene Therapy and Neuroscience.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Cordelier P, Van Bockstaele E, Calarota SA, et al., "Inhibiting AIDS in the central nervous system: gene delivery to protect neurons from HIV", Mol Ther. 2003 Jun;7(6):801-10.

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