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Journal of Virology, July 2003, p. 7957-7963, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7957-7963.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Delivery of Adeno-Associated Virus Vectors to the Fetal Retina: Impact of Viral Capsid Proteins on Retinal Neuronal Progenitor Transduction

Enrico M. Surace,1 Alberto Auricchio,2,3 Samuel J. Reich,1 Tonia Rex,1 Ernest Glover,1 Stacey Pineles,1 Waixing Tang,1 Erin O'Connor,1 Arkady Lyubarsky,1 Andrey Savchenko,1 Edward N. Pugh Jr.,1 Albert M. Maguire,1 James M. Wilson,2 and Jean Bennett1*

F. M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, Scheie Eye Institute,1 Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, Pennsylvania,2 Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy3

Received 23 January 2003/ Accepted 4 April 2003

The development of fetal ocular gene transfer may be useful as a therapeutic tool for the prevention of retinal genetic disorders with congenital or early clinical manifestations. In this study we explored the neural progenitor transduction patterns of adeno-associated virus (AAV) vectors following delivery to the developing retina. Recombinant vectors with the same genome carrying the enhanced green fluorescent protein (EGFP) transgene packaged in capsids of differing serotypes (serotypes 1, 2, and 5, termed AAV2/1, AAV2/2, and AAV2/5, respectively) were created. Delivery of the AAV vectors during early retinal development resulted in efficient and stable transduction of retinal progenitors. Vector surface proteins and the developmental status of the retina profoundly affected viral tropism and transgene distribution. The procedure is not detrimental to retinal development and function and therefore provides a safe delivery vehicle for potential therapeutic applications and a means of assessing the mechanisms of retina development and disease.

* Corresponding author. Mailing address: University of Pennsylvania, 310 Stellar Chance Building, 422 Curie Blvd., Philadelphia, PA 19104-6069. Phone: (215) 898-0915. Fax: (215) 573-7155. E-mail: jebennet{at}mail.med.upenn.edu.

Journal of Virology, July 2003, p. 7957-7963, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7957-7963.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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