Abstract

The research objective of this project is to investigate the interactions of adeno-associated virus with its host cell. The underlying hypothesis is that by understanding these interactions as they apply to the biology of the virus we can contribute to the use of AAV vectors for gene therapy. We focus on two areas of research; first is the characterization of two new AAV serotypes, AAV4 and AAV5. These new viral isolates are being studied both as natural mutations of other serotypes for understanding the biology of this genus of virus and as novel vectors for gene transfer. AAV4 and AAV5 each exhibit distinct mechanisms of cellular uptake compared with AAV2, and thus unique tissue tropisms. Our work has demonstrated improved transduction of airway lung cells and cell types within in the CNS. The second area of investigation addresses the mechanism by which the viral regulatory proteins alter the cellular environment in order to make it permissive for the viral life cycle. Current research has identified a number of cellular factors that interact with the viral regulatory proteins. The role of these proteins in the life cycle of the virus and their effect on cellular regulation are being investigated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000695-01
Application #
6413833
Study Section
(GTTB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Quinn, Kathrina; Brindley, Melinda A; Weller, Melodie L et al. (2009) Rho GTPases modulate entry of Ebola virus and vesicular stomatitis virus pseudotyped vectors. J Virol 83:10176-86
Craig, Anthony T; Gavrilova, Oksana; Dwyer, Nancy K et al. (2009) Transduction of rat pancreatic islets with pseudotyped adeno-associated virus vectors. Virol J 6:61
Vosters, Jelle L; Landek-Salgado, Melissa A; Yin, Hongen et al. (2009) Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjogren's syndrome. Arthritis Rheum 60:3633-41
Voutetakis, Antonis; Zheng, Changyu; Mineshiba, Fumi et al. (2007) Adeno-associated virus serotype 2-mediated gene transfer to the parotid glands of nonhuman primates. Hum Gene Ther 18:142-50
Voutetakis, A; Zheng, C; Wang, J et al. (2007) Gender differences in serotype 2 adeno-associated virus biodistribution after administration to rodent salivary glands. Hum Gene Ther 18:1109-18
Liu, Gumei; Chen, Yong Hong; He, Xiaohua et al. (2007) Adeno-associated virus type 5 reduces learning deficits and restores glutamate receptor subunit levels in MPS VII mice CNS. Mol Ther 15:242-7
Govindasamy, Lakshmanan; Padron, Eric; McKenna, Robert et al. (2006) Structurally mapping the diverse phenotype of adeno-associated virus serotype 4. J Virol 80:11556-70
Schmidt, Michael; Chiorini, John A (2006) Gangliosides are essential for bovine adeno-associated virus entry. J Virol 80:5516-22
Schmidt, Michael; Grot, Emmanuelle; Cervenka, Peter et al. (2006) Identification and characterization of novel adeno-associated virus isolates in ATCC virus stocks. J Virol 80:5082-5
Katano, H; Kok, M R; Cotrim, A P et al. (2006) Enhanced transduction of mouse salivary glands with AAV5-based vectors. Gene Ther 13:594-601

Showing the most recent 10 out of 37 publications