Thomas Weber, PhD
- ASSOCIATE PROFESSOR | Medicine, Cardiology
- ASSOCIATE PROFESSOR | Microbiology
- ASSOCIATE PROFESSOR | Cell, Developmental & Regenerative Biology
Research Topics:Cardiovascular, Cell Biology, Gene Therapy, Intracellular Transport, Protein Trafficking & Sorting, Regeneration, Viruses and Virology
Adeno-Associated Virus (AAV) Biology and AAV Gene Therapy
Gene therapy is a promising platform to treat and potentially cure currently intractable disorders. Among the most promising gene delivery vehicles are vectors based on adeno-associated virus (AAV).
AAV is particularly attractive because:
1) It is not known to be associated with any disease.
2) Recombinant AAV vectors can trigger long-term gene expression even in the absence of genome integration (at least in postmitotic tissues).
3) AVV vectors display only limited immunogenicity.
Due to these favorable properties, enthusiasm for gene therapy vectors based on adeno-associated virus (AAV) has steadily increased among researchers over the last few years. In fact, as of July 2015, 137 clinical trials using AAV have either been completed or are in progress. Moreover, the treatment of lipoprotein lipase deficiency with an AAV vector has been approved for clinical use in Europe, which is the first approval of gene therapeutic treatment in the Western World.
The research in our lab is focused on four areas:
1) The design of AAV variants with tissue and cell-specific tropism and increased resistance to pre-existing antibodies against the common AAV serotypes.
2) The development of AAV alternative approaches to overcome the hurdle that pre-existing anti-AAV antibodies pose to allow the use of AAV gene therapy for the broadest possible population segment.
3) To understand the basic biology of wild-type and recombinant AAV, especially as it relates to endocytosis and intracellular trafficking.