Generation of Complement Resistant Retroviral Vectors

The inactivation of retroviral vectors derived from murine cells in human serum represents a formidmany potential applications of in vivo retroviral-mediated gene therapy. We have recently demonstratof amphotropic retroviral vector particles in human serum is primarily mediated by complement activanatural antibody recognition of the alpha-galactosyl epitope on the retroviral envelope. Furthermoreretroviral particles in human serum was completely abolished when the interaction between anti- alphthis viral epitope was inhibited. The involvement of the alpha-galactosyl epitope in the inactivatiovector makes it a good target in the development of complement resistant vectors. Our aim is to deveparticles that are resistant to human complement-mediated inactivation. Specifically, we will investretroviral vector particles to survive in human serum when these particles are generated from producexpression of the alpha- galactosyl epitope is reduced or eliminated. Successful generation of complwill allow attempts at retroviral-mediated gene transfer experiments in vivo in applications where ccomplement system is unavoidable.