Gene Therapy
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April 1998, Volume 5, Number 4, Pages 531-536
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Paper
Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system
C Hofmann1 and M Strauss2,3

1HepaVec AG für Gentherapie, Berlin-Buch, Germany

2Humboldt University Berlin, Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany

3Danish Cancer Society, Division of Cancer Biology, Copenhagen, Denmark

Abstract

Baculovirus vectors are efficient tools for gene transfer into hepatocytes in vitro. However, gene transfer is strongly reduced in the presence of native sera, providing an explanation for the failure of direct application of the virus in vivo. In this study, we define the role of the complement (C) system (C) as a major cause for baculovirus inactivation in human serum. Baculoviruses most likely activate the classical pathway of the C system and assembly of very late C components is required for inactivation of the vector. We demonstrate the survival of baculovirus vectors in human serum through treatment with a functional blocking antibody against C component 5. Inactivation of baculovirus in human plasma and whole blood was prevented by treatment with cobra venom factor. The data reveal various interactions of baculovirus vectors with the C system and will lead to facilitation of baculovirus-mediated gene transfer into hepatocytes in vivo by protection of the vector from C inactivation.

Keywords

baculovirus vectors; complement system; complement inhibitors; hepatocytes; liver gene therapy

Received 19 September 1997; accepted 17 November 1997
April 1998, Volume 5, Number 4, Pages 531-536
Table of contents    Previous  Abstract  Next   Article  PDF