Cystic Fibrosis Research Today is a free monthly online journal that collates and summarizes the latest research about Cystic Fibrosis, including details on symptoms, genetics, treatment, information.

A defective nontransmissible recombinant Sendai virus mediates efficient gene transfer to airway epithelium in vivo.

Ferrari S, Griesenbach U, Shiraki-Iida T, Shu T, Hironaka T, Hou X, Williams J, Zhu J, Jeffery PK, Geddes DM, Hasegawa M, Alton EW

Department of Gene Therapy, National Heart & Lung Institute, Imperial College Faculty of Medicine, London, UK.

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/DeltaF). Here we show that SeV/DeltaF is able to mediate beta-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/DeltaF 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.

Published 27 October 2004 in Gene Ther, 11(22): 1659-64.
Full-text of this article is available online (may require subscription).

© 2004-2008 Cystic Fibrosis Research Today. All Rights Reserved.