This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our studies on ssDNA viruses are aimed at identifying structural determinants of receptor attachment, tissue tropism, in vivo pathogenicity, and transduction efficiencies between highly homologous Parvoviridae strains and serotypes. Our structural studies so far indicate that slight capsid surface alterations, resulting from amino acid differences, are associated with pronounced differences in biological properties during the viral life cycle of parvoviruses. Our long-term goals are to utilize the structural information obtained for the design of viral vaccines, foreign antigenic delivery systems, and viral gene therapy vectors for the treatment of animal and human diseases. We wish to obtain experimental beam time for data collection on the Adeno-associated virus serotypes AAV5, AAV8 and AAV9??""""""""being exploited for gene therapy applications and the prototype strain of minute virus of mice (MVMp).
We aim to collect native data on AAV9 for which there is no structural information, AAV5 and MVMp co-crystallized with sialylated trisaccharide components of their cell surface receptors and AAV8 and MVMp at pHs that mimic endosomal conditions. The structures of wt AAV5, AAV8 and MVMp have already been determined with data from various synchrotron sources, including X29 at NSLS.
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