Polyethylenimine coating to produce serum-resistant baculoviral vectors for in vivo gene delivery

Recombinant baculoviral vectors efficiently transduce many types of mammalian cells. However, their in vivo applications are hampered by the sensitivity of the virus to complement-mediated inactivation. Based on our observation that the surface charge of baculovirus is negative at neutral pH, we developed a procedure to coat baculoviral vectors with positively charged polyethylenimine 25 kDa, a commonly tested non-viral gene delivery vector, through electrostatic interaction. This coating was effective in protecting baculoviral vectors against human and rat serum-mediated inactivation in vitro, providing transduction efficiencies comparable with that generated by the control virus used under a serum-free condition. Enhanced in vivo gene expression in the liver and spleen was observed after tail vein injection of the coated viruses into mice. When injected directly into human tumor xenografts in nude mice, the coated viruses suppressed tumor development more effectively than uncoated viral vectors. These findings demonstrated the usefulness of using a simple coating method to circumvent a major obstacle to in vivo application of baculoviral vectors. The method may also serve as a flexible platform technology for improved use of the vectors, for example introducing a targeting ligand and minimizing immune responses.