Biocompatible polymer enhances the in vitro and in vivo transfection efficiency of HVJ envelope vector
Article first published online: 14 FEB 2005
Copyright © 2005 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 7, Issue 7, pages 888–897, July 2005
How to Cite
Mima, H., Tomoshige, R., Kanamori, T., Tabata, Y., Yamamoto, S., Ito, S., Tamai, K. and Kaneda, Y. (2005), Biocompatible polymer enhances the in vitro and in vivo transfection efficiency of HVJ envelope vector. J. Gene Med., 7: 888–897. doi: 10.1002/jgm.735
- Issue published online: 22 JUN 2005
- Article first published online: 14 FEB 2005
- Manuscript Accepted: 1 DEC 2004
- Manuscript Revised: 29 NOV 2004
- Manuscript Received: 18 AUG 2004
- non-viral vector;
- gene transfer;
- fusion-mediated delivery
Vector development is critical for the advancement of human gene therapy. However, the use of viral vectors raises many safety concerns and most non-viral methods are less efficient for gene transfer. One of the breakthroughs in vector technology is the combination of the vector with various polymers.
HVJ (hemagglutinating virus of Japan) envelope vector (HVJ-E) has been developed as a versatile gene transfer vector. In this study, we combined HVJ-E with cationized gelatin to make it a more powerful tool and assessed its transfection efficiency in vitro and in vivo. In addition, we investigated the mechanism of the gene transfer by means of the inhibition of fusion or endocytosis.
The combination of both protamine sulfate and cationized gelatin with HVJ-E, referred to as PS-CG-HVJ-E, further enhanced the in vitro transfection efficiency. In CT26 cells, the luciferase gene expression of PS-CG-HVJ-E was approximately 10 times higher than that of the combination of protamine sulfate with HVJ-E or the combination of cationized gelatin with HVJ-E, referred to as PS-HVJ-E or CG-HVJ-E, respectively. Furthermore, the luciferase gene expression in liver mediated by intravenous administration of CG-HVJ-E was much higher than the luciferase gene expression mediated by PS-HVJ-E or PS-CG-HVJ-E and approximately 100 times higher than that mediated by HVJ-E alone.
Cationized gelatin-conjugated HVJ-E enhanced gene transfection efficiency both in vitro and in vivo. These results suggest that low molecular weight cationized gelatin may be appropriate for complex formation with various envelope viruses, such as retrovirus, herpes virus and HIV. Copyright © 2005 John Wiley & Sons, Ltd.