Projects and Grants: An Overview
Adeno-associated virus (AAV)-based vectors are promising gene delivery vehicles that find widespread use in basic and preclinical research and, more recently, have been used in numerous clinical trials aimed at treating an array of diseases, ranging from genetic diseases, to cancer, to cardiovascular disorders, and others.
Despite the great promise of AAV-based vectors, the knowledge of many aspects of basic AAV virology remains limited, and further development of improved AAV-based vectors continues to be an area of active research. Our lab concentrates on two areas of AAV research:
Altering AAV tropism
Together, the AAV serotypes and variants display a large array of cell and tissue tropism. However, some tissues are more readily trasducible than others, and some cell types remain refractory to transduction. Furthermore, all of the serotypes transduce more than one tissue/cell type—albeit to varying degrees. Significantly, for many applications, an ideal AAV vector would transduce only one specific cell type/tissue.
Because of this, our lab works on the development of improved methods to both restrict and expand AAV tropism. A particular focus is the targeting of AAV both to cells of the cardiovascular system as well as to stem cells.
Biology of AAV entry
AAV is a small, non-enveloped, single-stranded DNA virus that has to deliver its DNA to the nucleus for a successful transduction/infection. While considerable progress has been made over the past decades in elucidating this multistep process, many details of both AAV endocytosis and intracellular trafficking of AAV remain unknown. Because of the importance of endocytosis and intracellular trafficking for AAV tropism, our lab works on three aspects of AAV biology:
- Identification of the cellular receptors of AAV serotypes
- Elucidation of the mechanism(s) of viral endocytosis
- Elucidation of the molecular mechanisms of trafficking of AAV from the cell periphery to the nucleus
Thomas Weber, PhD
Room AB 3-37
1428 Madison Avenue
New York, NY 10029