Research Interests: Molecular aspects of Adeno-associated virus genome packaging, and Optimization of AAV vector performance and production
The genome of AAV 2 is composed of 4679 bases of linear, single stranded DNA that is packaged into a 20nm viral particle comprised of 60 capsid protein subunits arranged in T=1 icosahedral symmetry. For a few ssDNA viruses, crystal structures have shown segments of ordered nucleic acid bound to sites on the inside surfaces of the coat proteins. The crystal structure of the AAV 2 capsid shows that the internal capside surface is highly contoured but it is not known if the packaged AAV genome sequences interact with the viral capsid proteins in a sequence specific manner.
One goal of the lab is to determine how nucleic acid is inserted into the
capsid, and if there are specific contacts formed between the AAV ssDNA genome and the capsid
proteins of wild-type virus by incorporating computer modeling techniques and making mutations
in the viral genome.
A second goal is to understand AAV virion assembly and capsid subunit interactions using computer modeling and by studying the infectivity and biochemical properties of capsid mutants. In addition to the study of AAV assembly and packaging, the lab is developing and optimizing production, purification, and testing methods for recombinant AAV vectors.
Developing the methods for producing new vectors, the scale-up of production methods for human trials, automation of manufacturing, and development of new assays are primary activities.
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