Department of Pediatrics, Division of Pulmonology; Gene Therapy Center
Biomedical Engineering and Bioengineering | Genetics and Genomics | Pulmonology | Therapeutics
Recombinant adeno-associated viral (rAAV) vectors have been widely used in pulmonary gene therapy research. In this study, we evaluated the transduction and expression efficiencies of several AAV serotypes and AAV2 capsid mutants with specific pulmonary targeting ligands in the mouse lung. The noninvasive intranasal delivery was compared with the traditional intratracheal lung delivery. The rAAV8 was the most efficient serotype at expressing alpha-1-antitrypsin (AAT) in the lung among all the tested serotypes and mutants. A dose of 1 x 1010 vg of rAAV8-CB-AAT transduced a high percentage of cells in the lung when delivered intratrachealy. The serum and the broncho-alveolar lavage fluid (BALF) levels of human AAT (hAAT) were about 6- and 2.5-fold higher, respectively, than those of rAAV5 group. Among the rAAV2 capsid mutants, the rAAV2 capsid mutants that display a peptide sequence from hAAT ("long serpin") indicated a twofold increase in transgene expression. For most vectors, the serum hAAT levels achieved after intranasal delivery were 1/2 to 1/3 of those with the intratracheal method. Overall, rAAV8 was the most promising vector for the future application in gene therapy of pulmonary diseases such as AAT deficiency-related emphysema.
DOI of Published Version
Mol Ther. 2009 Jan;17(1):81-87. doi: 10.1038/mt.2008.217. Epub 2016 Dec 6. Link to article on publisher's site
Molecular therapy : the journal of the American Society of Gene Therapy
Liqun Wang R, McLaughlin TJ, Cossette T, Tang Q, Foust K, Campbell-Thompson M, Martino A, Cruz P, Loiler S, Mueller C, Flotte TR. (2009). Recombinant AAV Serotype and Capsid Mutant Comparison for Pulmonary Gene Transfer of alpha-1-Antitrypsin Using Invasive and Noninvasive Delivery. Open Access Articles. https://doi.org/10.1038/mt.2008.217. Retrieved from https://escholarship.umassmed.edu/oapubs/3037
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