Incorporation of decay-accelerating factor into the baculovirus envelope generates complement-resistant gene transfer vectors

Baculovirus vectors are an efficient means to deliver genes into hepatocyte s in vitro. In experiments that exclude components of the complement system , gene transfer is facilitated. Therefore, the complement system has been d efined to represent a potent primary barrier to direct application of bacul oviruses in vivo. Here we have genetically manipulated baculoviruses so tha t the complement-regulatory protein human decay-accelerating factor (DAF) i s incorporated into the viral envelope. We found that this modification pro tected baculovirus vectors against complement-mediated inactivation. Comple ment-resistant baculovirus vectors were additionally analyzed by immunoblot ting and electron microscopy, showing the extent of envelope-incorporated D AF and shape of complement-resistant baculoviruses after exposure to comple ment. This modified baculovirus vector allowed for an enhanced gene transfe r into complement-sufficient neonatal rats in vivo, and thus represents a s tep in the development of improved alternative viral Vectors for gene thera py.