Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system.
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.
Hofmann
C
C
HepaVec AG für Gentherapie, Berlin-Buch, Germany.
Strauss
M
M
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016367:Baculoviridae; D002478:Cells, Cultured; D003167:Complement Activation; D015936:Complement C5a / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008099:Liver / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D003169:Complement Inactivator Proteins; D015936:Complement C5a