体内外慢病毒介导的气道上皮祖细胞的转导

Title:Ex Vivo and In Vivo Lentivirus-Mediated Transduction of Airway Epithelial Progenitor Cells

Volume: 15 Issue: 6

Author(s): Giulia Leoni, Marguerite Y. Wasowicz, Mario Chan, Cuixiang Meng, Raymond Farley and Steven L. Brody, Makoto Inoue, Mamoru Hasegawa, Eric W.F.W. Alton and Uta Griesenbach

Affiliation:

关键词: 囊肿性纤维化，基因治疗，慢病毒，祖基底细胞，Polidocanol。

摘要: A key challenge in pulmonary gene therapy for cystic fibrosis is to provide long-term correction of the genetic defect. This may be achievable by targeting airway epithelial stem/progenitor cells with an integrating vector. Here, we evaluated the ability of a lentiviral vector, derived from the simian immunodeficiency virus and pseudotyped with F and HN envelope proteins from Sendai virus, to transduce progenitor basal cells of the mouse nasal airways. We first transduced basal cell-enriched cultures ex vivo and confirmed efficient transduction of cytokeratin-5 positive cells. We next asked whether progenitor cells could be transduced in vivo. We evaluated the transduction efficiency in mice pretreated by intranasal administration of polidocanol to expose the progenitor cell layer. Compared to control mice, polidocanol treated mice demonstrated a significant increase in the number of transduced basal cells at 3 and 14 days post vector administration. At 14 days, the epithelium of treated mice contained clusters (4 to 8 adjacent cells) of well differentiated ciliated, as well as basal cells suggesting a clonal expansion. These results indicate that our lentiviral vector can transduce progenitor basal cells in vivo, although transduction required denudation of the surface epithelium prior to vector administration.

Cite this article as:

Giulia Leoni, Marguerite Y. Wasowicz, Mario Chan, Cuixiang Meng, Raymond Farley and Steven L. Brody, Makoto Inoue, Mamoru Hasegawa, Eric W.F.W. Alton and Uta Griesenbach , Ex Vivo and In Vivo Lentivirus-Mediated Transduction of Airway Epithelial Progenitor Cells, Current Gene Therapy 2015; 15 (6) . https://dx.doi.org/10.2174/1566523215666151016123625