Dr. Kappes' research is focused on studying the molecular biology of the human immunodeficiency virus type 1 (HIV-1), and the development of lentiviral-based vectors for gene delivery. These studies are helping to understand how infectious virions are formed and how the viral enzymes [reverse transcriptase (RT) and integrase (IN)], function during the early stages of the virus life cycle. By using virion associated HIV accessory proteins (Vpr and Vpx), Dr. Kappes has developed an approach for incorporating functional RT and IN into virions independently of the normal Gag-Pol packaging pathway. This has uncoupled the RT and IN function from Gag-Pol function and enabled, for the first time, a detailed molecular analysis of reverse transcription and integration in the context of replicating virus (in vivo). Based on the principles of incorporating RT and IN in trans, Dr. Kappes has developed a new generation of HIV/lentiviral-based vectors for gene therapy. Lentiviral vectors appear to be well suited for gene therapy since they can transduce nondividing (somatic) cells. By separating the expression of RT and IN from the other vector components it is possible to produce lentiviral vectors with minimal risk of recombination and the generation of replication competent virus.
