Perfluorochemical liquid enhances adeno-associated virus-mediated transgene expression in lungs.
Use of adeno-associated virus (AAV) vectors for lung gene therapy is limited, in part, by low levels of AAV-mediated transgene expression in lungs. Generally, less than 1% of total airway and alveolar epithelial cells express transgene activity following vector administration. A means of improving AAV vector delivery could potentially enhance AAV-mediated gene expression in lungs. We have previously demonstrated that use of perfluorochemical (PFC) liquids improved overall levels of adenovirus vector-mediated gene expression as well as distribution of expression in lungs of spontaneously breathing rodents. To evaluate whether use of PFC liquids might similarly enhance AAV-mediated expression, spontaneously breathing rodents received intratracheal instillation of the AAV vectors CWRAP and ARAP4 (2-5 x 10(8) FFU/animal) with or without 10 cc/kg body wt PFC liquid (FC-75, ACROS). Animals were sacrificed 4 weeks later and lungs assessed for overall and in situ alkaline phosphatase ( AP) expression. Animals receiving vector alone exhibited scattered sparse in situ activity, predominantly in alveolar epithelium. In contrast, animals receiving vector with FC-75 exhibited increased and more widespread AP expression as well as up to a 26-fold increase in AP activity. These results demonstrate that use of the PFC liquid FC-75 improves overall and in situ AAV-mediated gene expression in rodent lungs.[1]References
- Perfluorochemical liquid enhances adeno-associated virus-mediated transgene expression in lungs. Weiss, D.J., Bonneau, L., Allen, J.M., Miller, A.D., Halbert, C.L. Mol. Ther. (2000) [Pubmed]
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