PuSH - Publication Server of Helmholtz Zentrum München: Adeno-associated virus serotype 9-mediated pulmonary transgene expression: effect of mouse strain, animal gender and lung inflammation.

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Pfeifer, C.* ; Aneja, M.K. ; Hasenpusch, G.* ; Rudolph, C.*

Adeno-associated virus serotype 9-mediated pulmonary transgene expression: effect of mouse strain, animal gender and lung inflammation.

Gene Ther. 18, 1034-1042 (2011)

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Gene therapy holds great potential for the treatment of various acquired and inherited pulmonary diseases. Among various viral vectors, adeno-associated viral (AAV) vectors have been most frequently used in different clinical trials of pulmonary gene therapy. In the present study, we examined the kinetics and duration of transgene expression, vector biodistribution and development of neutralizing antibodies (NAB) in mice after pulmonary application of AAV2/9 vector. The pulmonary route of application did not affect any of the measured parameters. Transgene expression and biodistribution analysis at day 450 post-application confirmed the systemic spread of the vector after pulmonary delivery. Using SPB(-/-) mice, the study shows that AAV2/9-mediated gene expression is influenced by animal gender but not mouse genotype and is insensitive to the presence of lung inflammation. Lower expression levels were observed in male compared with female mice, and transient immunosuppression with dexamethasone significantly reduced the development of NAB in both genders of mice. The study thus advances this serotype for further development and use as a therapeutic vector.

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