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Journal of Virology, August 2008, p. 7711-7715, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00542-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Biodistribution and Safety Profile of Recombinant Adeno-Associated Virus Serotype 6 Vectors following Intravenous Delivery {triangledown}

Daniel Stone ,1,{dagger},{ddagger} Ying Liu,1,{dagger} Zong-Yi Li,1 Robert Strauss,1 Eric E. Finn,3 James M. Allen,3 Jeffrey S. Chamberlain,3 and André Lieber1,2*

Division of Medical Genetics, Department of Medicine,1 Department of Pathology,2 Department of Neurology, University of Washington, Seattle, Washington 981953

Received 11 March 2008/ Accepted 6 May 2008

Recombinant adeno-associated virus vectors based on serotype 6 (rAAV6) efficiently transduce skeletal muscle after intravenous administration and have shown efficacy in the mdx model of muscular dystrophy. As a prelude to future clinical studies, we investigated the biodistribution and safety profile of rAAV6 in mice. Although it was present in all organs tested, rAAV6 was sequestered mainly in the liver and spleen. rAAV6 had a minimal effect on circulating blood cells and caused no apparent hepatotoxicity or coagulation activation. rAAV6 caused some neutrophil infiltration into the liver, with a transient elevation in cytokine and chemokine transcription/secretion. In summary, rAAV6 induces transient toxicity that subsides almost completely within 72 h and causes no significant side effects.

* Corresponding author. Mailing address: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195. Phone: (206) 221-3973. Fax: (206) 685-8675. E-mail: lieber00{at}u.washington.edu

{triangledown} Published ahead of print on 14 May 2008.

{dagger} D.S. and Y.L. contributed equally to this study.

{ddagger} Present address: California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720.

Journal of Virology, August 2008, p. 7711-7715, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00542-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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