SUICIDE GENE THERAPY FOR AIDS

University Of Colorado Denver, Aurora CO

Investigators

Abstract

This proposal outlines the continuing development of toxin gene therapy for Acquired Immune Deficiency Syndrome (AIDS), based on regulated expression of a diphtheria toxin A (DT-A) gene. Plasmid an retroviral constructs were generated from which DT-A expression was controlled by HIV-1 regulatory proteins Tat and Rev. Stable cell lines were derived which had been transfected or infected with DT-A-encoding plasmids and retroviruses, respectively. Such cell lines showed a markedly impaired ability to produce HIV, especially those infected with DT-A retrovirus, which were resistant to infection by HIV, especially those infected with DT-A retrovirus, which were resistant to infection by HIV strain IIIb over at least a four day period. We now propose to examine the HIV resistance conferred by the DT-A retrovirus in more detail over a longer time course, and to improve the efficiency with which HIV-resistant cells are obtained. We will examine HIV resistance in systems selected to model, as closely as possible, in vivo HIV infection. We hope to demonstrate efficient inducibility of DT-A expression in HIV-infected cells, and cell death before substantial HIV production.