Protection of baculovirus vectors expressing complement regulatory proteins against serum complement attack

Abstract

Baculovirus vectors (BVs) enable safe and efficient gene delivery to mammalian cells and are useful in a wide range of applications, including gene therapy and in vivo analysis of gene functions. We previously developed BVs expressing malaria sporozoite surface proteins for targeting liver cells or hepatocytes. However, BVs are known to be very vulnerable to complement attack and efforts to overcome their inactivation based on complement are important. In this study, BVs expressing complement regulatory proteins (CRPs) on the surfaces of virions were developed to inhibit complement reactions. Decay accelerating factor (DAF; CD55)- type BVs exhibited significantly higher complement resistance than control BVs without any CRPs in HepG2 cells transduction, although the transduction efficacy of DAF-type BV was low. In contrast, CD46-DAFCD59 fusion type BVs showed significantly higher transduction efficacy and complement resistance than both control and DAF-type BVs. DAF-type and CD46-DAF-CD59 type BVs repressed formation of the membrane attack complex, a terminal product of complement reaction cascades, induced by BVs. These results suggest that the CD46-DAF-CD59 fusion construct confers complement protection ability superior to that of the DAF construct in gene delivery under complement active serum.