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Journal of Virology, July 2006, p. 6603-6611, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.00528-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Enhanced Baculovirus-Mediated Transduction of Human Cancer Cells by Tumor-Homing Peptides

Anna R. Mäkelä,1,{dagger} Heli Matilainen,1,{dagger} Daniel J. White,1 Erkki Ruoslahti,2 and Christian Oker-Blom1*

NanoScience Center, Department of Biological and Environmental Science, P.O. Box 35, 40014 University of Jyväskylä, Finland,1 Burnham Institute for Medical Research, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 931062

Received 14 March 2006/ Accepted 20 April 2006

Tumor cells and vasculature offer specific targets for the selective delivery of therapeutic genes. To achieve tumor-specific gene transfer, baculovirus tropism was manipulated by viral envelope modification using baculovirus display technology. LyP-1, F3, and CGKRK tumor-homing peptides, originally identified by in vivo screening of phage display libraries, were fused to the transmembrane anchor of vesicular stomatitis virus G protein and displayed on the baculoviral surface. The fusion proteins were successfully incorporated into budded virions, which showed two- to fivefold-improved binding to human breast carcinoma (MDA-MB-435) and hepatocarcinoma (HepG2) cells. The LyP-1 peptide inhibited viral binding to MDA-MB-435 cells with a greater magnitude and specificity than the CGKRK and F3 peptides. Maximal 7- and 24-fold increases in transduction, determined by transgene expression level, were achieved for the MDA-MB-435 and HepG2 cells, respectively. The internalization of each virus was inhibited by ammonium chloride treatment, suggesting the use of a similar endocytic entry route. The LyP-1 and F3 peptides showed an apparent inhibitory effect in transduction of HepG2 cells with the corresponding display viruses. Together, these results imply that the efficiency of baculovirus-mediated gene delivery can be significantly enhanced in vitro when tumor-targeting ligands are used and therefore highlight the potential of baculovirus vectors in cancer gene therapy.

* Corresponding author. Mailing address: NanoScience Center, Department of Biological and Environmental Science, P.O. Box 35, FIN-40014 University of Jyväskylä, Finland. Phone: 358 14 260 2285. Fax: 358 14 260 2221. E-mail: okerblom{at}jyu.fi.

{dagger} A.M. and H.M. made equal contributions to this article.

Journal of Virology, July 2006, p. 6603-6611, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.00528-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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