Adeno-associated virus serotype 9 vectors transduce murine alveolar and nasal epithelia and can be readministered
- 29 August 2006
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 103 (35), 12993-12998
- https://doi.org/10.1073/pnas.0601433103
Abstract
Airway-directed gene transfer has emerged as a promising approach for the treatment of the two genetic diseases of the lung, namely cystic fibrosis and α-1-antitrypsin deficiency. Herein we describe the transduction efficiency of a novel adeno-associated virus (AAV) vector, AAV2/9, across murine nasal and lung airway epithelia. At the peak of gene expression AAV2/9-mediated human α-1-antitrypsin gene expression in serum was ≈60-fold better than that of AAV2/5. We found that AAV2/9-mediated nLacZ gene transfer in nasal and lung airways was relatively stable for 9 months, suggesting that a progenitor airway cell population was transduced. Most interestingly, we show that AAV2/9 can be readministered in the presence of high levels of serum-circulating neutralizing antibodies as early as 1 month after initial exposure, with minimal effect on overall reporter gene expression, rendering it a promising gene transfer vector candidate for use in humans.This publication has 30 references indexed in Scilit:
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