Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 35, Pages 12993-12998Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0601433103
Keywords
long-term expression; lung
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Funding
- NHLBI NIH HHS [P01 HL051746, P01-HL051746] Funding Source: Medline
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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 alpha-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 alpha-1-antitrypsin gene expression in serum was approximate to 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.
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