Efficient retroviral gene transfer of a Tat-regulated herpes simplex virus thymidine kinase gene for HIV gene therapy

We have previously reported that lymphoid and monocytic CD4+ cells transfected with and expressing a herpes simplex virus thymidine kinase (HSV-TK) gene, under the transcriptional control of the HIV long terminal repeat, are protected from HIV spread in the presence of 10 μM acyclovir. Furthermore, the expression of HSV-TK was able to enhance the antiviral effect of AZT. We now investigate the ability of retroviral vectors containing the HSV-TK gene under the transcriptional control of HIV regulatory sequences to transduce target cells. Bone marrow cells or lymphocytes might be genetically modified by these vectors in an HIV gene therapy strategy. In this study, we describe high-titer retroviral producer clones expressing the HSV-TK gene from an HIV LTR. Lymphoid cells transduced with one of these retroviruses express HSV-TK at a relatively low basal level. When the same cells express the HIV regulatory protein Tat, they are 10-fold more sensitive to killing by ganciclovir. Thus, this vector has potential application for gene therapy of HIV infection.