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Journal of Virology, February 2008, p. 1399-1406, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.02012-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Adeno-Associated Virus Type 12 (AAV12): a Novel AAV Serotype with Sialic Acid- and Heparan Sulfate Proteoglycan-Independent Transduction Activity{triangledown}

Michael Schmidt, Antonis Voutetakis, Sandra Afione, Changyu Zheng, Danielle Mandikian, and John A. Chiorini*

Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892

Received 11 September 2007/ Accepted 13 November 2007

Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy. Recent isolations of novel AAV serotypes have led to significant advances by broadening the tropism and increasing the efficiency of gene transfer to the desired target cell. However, a major concern that remains is the strong preexisting immune responses to several vectors. In this paper, we describe the isolation and characterization of AAV12, an AAV serotype with unique biological and immunological properties. In contrast to those of all other reported AAVs, AAV12 cell attachment and transduction do not require cell surface sialic acids or heparan sulfate proteoglycans. Furthermore, rAAV12 is resistant to neutralization by circulating antibodies from human serum. The feasibility of rAAV12 as a vector was demonstrated in a mouse model in which muscle and salivary glands were transduced. These characteristics make rAAV12 an interesting candidate for gene transfer applications.

* Corresponding author. Mailing address: NIH 10/1N113, 10 Center Dr., MSC1190, Bethesda, MD 20892. Phone: (301) 496-4279. Fax: (301) 402-1228. E-mail: jchiorini{at}dir.nidcr.nih.gov

{triangledown} Published ahead of print on 28 November 2007.

Journal of Virology, February 2008, p. 1399-1406, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.02012-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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