Original Article

Gene Therapy (2006) 13, 304–312. doi:10.1038/sj.gt.3302657; published online 3 November 2005

Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo

M U Kaikkonen1,2,5, J K Räty1,2,5, K J Airenne1,2, T Wirth1,2, T Heikura1,2 and S Ylä-Herttuala1,3,4

  1. 1AI Virtanen Institute, Department of Biotechnology and Molecular Medicine, University of Kuopio, Kuopio, Finland
  2. 2Ark Therapeutics Oyj, Neulaniementie, Kuopio, Finland
  3. 3Department of Medicine, Kuopio University, Kuopio, Finland
  4. 4Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland

Correspondence: S Ylä-Herttuala, AI Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland. E-mail: Seppo.Ylaherttuala@uku.fi

5These authors contributed equally to this work.

Received 6 July 2005; Revised 16 August 2005; Accepted 18 August 2005; Published online 3 November 2005.

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Abstract

Pseudotyping of viral vectors has been widely used to enhance viral transduction efficiency. One of the most popular pseudotyping proteins has been the G-protein of the vesicular stomatitis virus, VSV-G. In the present study, we show that the 21-amino-acid ectodomain with transmembrane and cytoplasmic tail domains of VSV-G (VSV-GED) augments baculovirus-mediated gene delivery in vertebrate cells by aiding viral entry. The VSV-GED pseudotyped virus replicated efficiently in insect cells yielding high titers. Five out of six studied cell lines showed improved transduction, as measured by a number of transduced cells or transgene expression level. Nearly 15-fold increase in the transduction efficiency was detected in rat malignant glioma cells as compared to the control virus. In the rat brain, transgene expression could be detected in the walls of lateral ventricles and in subarachnoid membranes. Increased transduction efficiency was also observed in the rabbit muscle. Our results suggest that VSV-GED enhances baculoviral gene transfer by augmenting gp64-mediated endosomal release. Moreover, no cytotoxicity was associated with improved gene transfer efficiency. Thus, VSV-GED pseudotyping provides a simple means to enhance baculovirus-mediated gene transfer in vitro and in vivo.

Keywords:

baculovirus, VSV-GS, VSV-G, pseudotyping