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Neutralizing antibodies against AAV serotypes 1, 2, 6, and 9 in sera of commonly used animal models.

Mol Ther.. 2010-01;  20(1):73-83
Rapti K, Louis-Jeune V, Kohlbrenner E, Ishikawa K, Ladage D, Zolotukhin S, Hajjar RJ, Weber T. 1Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA; 2Department of Pediatrics, University of Florida, Gainesville, Florida, USA
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摘要

Adeno-associated virus (AAV)-based vectors are promising gene delivery vehicles for human gene transfer. One significant obstacle to AAV-based gene therapy is the high prevalence of neutralizing antibodies in humans. Until now, it was thought that, except for nonhuman primates, pre-existing neutralizing antibodies are not a problem in small or large animal models for gene therapy. Here, we demonstrate that sera of several animal models of cardiovascular diseases harbor pre-existing antibodies against the cardiotropic AAV serotypes AAV1, AAV6, and AAV9 and against AAV2. The neutralizing antibody titers vary widely both between species and between serotypes. Of all species tested, rats displayed the lowest levels... More

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