HVJ (Sendai virus)-cationic liposomes: a novel and potentially effective liposome-mediated technique for gene transfer to the airway epithelium (original) (raw)
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- Published: 01 July 1997
Gene Therapy volume 4, pages 631–638 (1997)Cite this article
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Abstract
We designed a novel technique for targeted gene transfer into the airway epithelium. This was constructed using multilamellar cationic liposomes, containing N-(α-trimethylammonioacetyl)-didodecyl- D ox-glutamate chloride, phosphatidylcholine and cholesterol and fused with haemagglutinating virus of Japan (HVJ), namely HVJ cationic liposomes. Single aerosol delivery of this novel vector to the airway of rats led to a highly efficient and widespread transduction of fluorescein isothiocyanate-labeled oligonucleotides or lacZ gene into the bronchial epithelium and alveolar macrophages, but not into the alveolar epithelium. The efficiency of gene transfer to the airway epithelium with a single administration of the lacZ gene was about 47.6% in the trachea, 39.0% in the bronchi and proximal bronchioli, and 2.9% in the terminal bronchioli, respectively (mean value, n = 6). Expression level of the luciferase gene delivered with this novel system was much higher than that without HVJ, in both the trachea and lung tissue. Two pretreatment HVJ-cationic liposome vehicles every other week resulted in minimal inflammatory infiltration in the subepithelial layer with no significant reduction in efficiency of the following gene transfer. We propose that this novel HVJ cationic liposome-mediated gene transfer system may be suitable for clinical gene therapy to treat subjects with lethal lung diseases such as cystic fibrosis.
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Authors and Affiliations
- Department of Pathology I, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Y Yonemitsu, T Yoshizumi & K Sueishi - Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Y Yonemitsu, T Yoshizumi & K Sugimachi - Institute for Molecular and Cellular Biology, Osaka University, Japan
Y Kaneda - Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan
A Muraishi
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Yonemitsu, Y., Kaneda, Y., Muraishi, A. et al. HVJ (Sendai virus)-cationic liposomes: a novel and potentially effective liposome-mediated technique for gene transfer to the airway epithelium.Gene Ther 4, 631–638 (1997). https://doi.org/10.1038/sj.gt.3300463
- Received: 20 September 1996
- Accepted: 11 April 1997
- Issue Date: 01 July 1997
- DOI: https://doi.org/10.1038/sj.gt.3300463