495. Efficient In Vivo Transduction of Mouse Airway Epithelial Cells by the Simian Immunodeficiency Virus Vector Pseudotyped with Sendai Virus F and HN Proteins

Although airways are important targets for gene therapy for diseases such as cystic fibrosis or asthma, few vectors can transduce these organs. Recombinant Sendai virus (SeV) vectors can easily penetrate the mucus layer and efficiently transduce airway epithelial cells from apical side. However, the expression of transgene by the vectors of present design is transient and generally lasts only for several days. To improve lentivirus entry into airway epithelial cells, we have attempted to make the novel pseudotyped Simian Immunodeficiency Virus (SIV) vector with SeV envelope proteins, F and HN. The SIV vector could not be pseudotyped with the intact F and HN, but could be successfully pseudotyped after modification of the cytoplasmic portion of both proteins (Kobayashi et al. ASGT 2002). The new F and HN pseudotyped SIV vector was produced to the titers of more than 10 6 TU/ml and could be easily concentrated by centrifugation. When 108 TU of SIV pseudotyped with F and HN was administered to mouse lungs through "sniffing", distinct transgene (GFP) expression was detected in the alveolar epithelium (Figure 1) and bronchiolar epithelial cells (Figure 2) ten days after the transduction. In contrast, VSV-G pseudotyped SIV vectors did not transduce the lung. These results suggest that our novel pseudotyped SIV vector with F and HN may be of great value as a tool for gene therapy of respiratory diseases.