- The ultimate goal of the Gene Therapy Center is to facilitate the progression and translation of gene therapy research from the laboratory bench into Phase I clinical trials for the treatment of human disease.
Our research focuses on the study of the dependent parvovirus adeno-associated virus. AAV is the only known DNA animal virus which requires co-infection by a second unrelated virus in order to undergo productive infection. The DNA tumor viruses, adenovirus and herpes simplex virus provide the necessary helper functions for AAV. AAV not only utilizes gene products from these tumor viruses, but it interferes with their growth and with oncogenicity of cells transformed by these viruses. In the absence of a helper virus, AAV is able to integrate into host cell DNA and maintain a latent infection. Superinfection of these cells with a helper virus results in the rescue and replication of the AAV genome. The ability of AAV to integrate and maintain itself in host cells and subsequent rescue and replication of its viral sequences is of considerable interest. In some respects, this behavior is similar to phenomena observed with bacterial transposons, yeast movable genetic elements, Drosophila copia sequences, P elements, and the RNA tumor viruses. For this reason AAV has recently been described as a type of replicating transposon. We have cloned the AAV genome into the bacterial plasmid pBR322 and demonstrated that this recombinant clone is infectious when introduced into human cells co-infected with a helper virus. This recombinant clone has provided a manipulatable system for the analysis of mechanism(s) involved in excision and integration of the adeno-associated virus genome. Based on these observations, we have been able to test AAV as a alternative viral vector for gene delivery. The ability to generate non-pathogenic viral vectors for current basic research have the long term potential of serving as reagents for use in clinical settings. We have established successful and long term gene expression over a year, which directly addresses the issue of molecular therapy required for genetic disorders. One of our current goals of research is to continue to derive delivery systems for use in gene therapy.