AAV-Mediated Gene Transfer to Mouse Lungs
The ability of adeno-associated viral (AAV) vectors to promote persistent gene expression in nondividing cells in multiple somatic tissues of animals (1, 2, 3, 4) makes them excellent tools for gene transfer. One tissue of interest for gene transfer is the lung epithelium, which is afflicted in cystic fibrosis (CF). However, although initial animal studies done with vectors based on A AV type 2 have demonstrated transduction in multiple cells types in the lung, the rates were modest in alveolar cells and much lower rates in airway epitheila and required high particle numbers (5, 6, 7). In contrast, an AAV6 encapsidated vector showed preferential transduction of epithelial cells in large and small airways (8) at rates that exceeded the 5% efficiency rate predicted to have a therapeutic value for CF gene therapy (9). In fact, recent studies using vectors based on other A AV types showed that types 1–6 have different tissue tropisms (10, 11, 12, 13, 14, 15), and that types 5 and 6 are more efficient than type 2 in lung epithelium (8,14). In mouse lung, an AAV2 vector gave modest transduction rates.
KeywordsMouse Lung Nitro Blue Tetrazolium Transduction Efficiency Alveolar Cell AAV2 Vector
- 3.Muzyczka, N. (1992) Use of adeno-associated virus as a general transduction vector for mammalian cells. Curr. Topics Microbiol. Immunol. 158, 97–129.Google Scholar
- 16.Chiorini, J. A., Yang, L., Liu, Y., Safer, B., and Kotin, R. M. (1997) Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles. J. Virol. 86, 6823–6833.Google Scholar
- 22.Sambrook, J., Fritsch, E. F., and Maniatis T. (1989) Molecular Cloning: A Laboratory Manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.Google Scholar