My lab studies replication and integration of Adeno-Associated Virus (AAV), structure/function of carbonic anhydrase (CA), and gene therapy for phenylketonuria (PKU). AAV, a small DNA virus, requires co-infection with helper virus for replication. Without helper, AAV integrates into human chromosome 19. My lab is defining the cellular requirements for AAV replication and integration, as well as characterizing the AAV Rep protein. My lab has cloned nine mammalian CA genes and made many amino acid mutations. This work has allowed use to analyze structure-function relationships, especially proton transfer. Experiments leading to a CAIII knockout mouse and isozyme specific inhibitors are in progress. Finally, my laboratory has cloned the gene for phenylalanine hydroxylase (PAH), developed AAV-based vectors expressing PAH and successfully cured PKU in the PAHEnu2 mouse models. The ultimate goal is human clinical trials. |
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