1. ¹Department of Gene Therapy, National Heart & Lung Institute, Imperial College Faculty of Medicine, London, UK
2. ²DNAVEC Corporation, Tsukuba-city, Ibaraki, Japan
3. ³UK Cystic Fibrosis Gene Therapy Consortium, UK

Correspondence: Dr U Griesenbach, Department of Gene Therapy, National Heart & Lung Institute, Imperial College Faculty of Medicine, 1B Manresa Road, SW3 6LR, London, UK

Received 22 March 2004; Accepted 26 May 2004; Published online 29 July 2004.

Abstract

Recombinant Sendai virus (SeV)-mediated gene transfer to differentiated airway epithelial cells has shown to be very efficient, because of its ability to overcome the intra- and extracellular barriers known to limit gene delivery. However, this virus is transmission competent and therefore unlikely to be suitable for use in clinical trials. A nontransmissible, replication-competent recombinant SeV has recently been developed by deleting the envelope Fusion (F) protein gene (SeV/F). Here we show that SeV/F is able to mediate -galactosidase reporter gene transfer to the respiratory tract of mice in vivo, as well as to human nasal epithelial cells in vitro. Further, in an ex vivo model of differentiated airway epithelium, SeV/F gene transfer was not importantly inhibited by native mucus. When compared to the transmission-competent SeV in vivo, no difference in gene expression was observed at the time of peak expression. The development of an F-defective nontransmissible SeV, which can still efficiently mediate gene transfer to the airway epithelium, represents the first important step towards the use of a cytoplasmic RNA viral vector in clinical trials of gene therapy.