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Journal of Virology, February 2003, p. 2768-2774, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2768-2774.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Characterization of Tissue Tropism Determinants of Adeno-Associated Virus Type 1

Bernd Hauck and Weidong Xiao*

Department of Pediatrics, University of Pennsylvania Medical Center, and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104

Received 2 August 2002/ Accepted 14 November 2002

Muscle is an attractive target for gene delivery because of its mass and because vectors can be delivered in a noninvasive fashion. Adeno-associated virus (AAV) has been shown to be effective for muscle-targeted gene transfer. Recent progress in characterization of AAV serotype 1 (AAV1) and AAV6 demonstrated that these two AAV serotypes are far more efficient in transducing muscle than is the traditionally used AAV2. Since all cis elements are identical in these vectors, the potential determinants for their differences in transducing muscle appear to be located within the AAV capsid proteins. In the present study, a series of AAV capsid mutants were generated to identify the major regions affecting AAV transduction efficiency in muscle. Replacement of amino acids 350 to 736 of AAV2 VP1 with the corresponding amino acids from VP1 of AAV1 resulted in a hybrid vector that behaved very similarly to AAV1 in vitro and in vivo in muscle. Characterization of additional mutants carrying smaller regions of the AAV1 VP1 amino acid sequence in the AAV2 capsid protein suggested that amino acids 350 to 430 of VP1 function as a major tissue tropism determinant. Further analysis showed that the heparin binding domain and the major antigenic determinants in the AAV capsid region were not necessary for the efficiency of AAV1 transduction of muscle.

* Corresponding author. Mailing address: 302 G Abramson Research Center, Children's Hospital of Philadelphia, 3516 Civic Center Blvd., Philadelphia, PA 19104. Phone: (215) 590-9170. Fax: (215) 590-9939. E-mail: wxiao{at}mail.med.upenn.edu.

Journal of Virology, February 2003, p. 2768-2774, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2768-2774.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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