Richard Morgan's laboratory focuses on the development of gene transfer technology with an emphasis on the applications to certain diseases, one of which is HIV disease. Retroviral vectors were constructed that inhibit the HIV-1 virus at various points in the viral life cycle with the main focus of inhibiting Tat/TAR and Rev/RRE functions. The goal of this work is to develop the components of the ideal anti-HIV vector. This ideal vector would potentially attack HIV at multiple points in the viral life cycle. Dr. Morgan's laboratory produced retroviral vectors that individually attack one or more of these points. These vectors include: sCD4 and CD4IgG binding decoy vectors, anti-sense Tat, antisense TAR, antisense Tat/Rev, Rev transdominant vectors, a CD4-KDEL ER retention signal vector, and a series of HIV inducible vectors that synthesize diphtheria toxin, cytosine deaminase, or interferon. New vectors are under analysis that express anti-HIV ribozymes and transdominant GAG proteins. Dr. Morgan's group has used these vectors to engineer T-cell lines, primary culture PBL and human CD34+ hematopoietic progenitor-enriched cells. All vectors can to varying amounts, inhibit both laboratory strains of HIV and clinical isolates. The comparison of these different vectors demonstrates consistent better protection with Rev transdominant vectors than any other vector analyzed in vitro. To evaluate these anti-HIV-1 vectors in humans, Dr. Morgan's laboratory has proposed a clinical trial in which CD4+ PBL derived from an HIV-1 negative twin will be engineered and then infused into the HIV-1+ twin. It is hoped that the anti-HIV engineered CD4 T-cells will not be killed by HIV and may have a longer life span in patients. This may potentially benefit the patients by stabilizing the immune system decline associated with HIV disease. The clinical trial is expected to start in the first half of 1996.
