Cell targeting with retroviral vector particles containing antibody-envelope fusion proteins

Abstract

Retroviral vectors are the most efficient tool to introduce genes into vertebrate cells. However, their use is limited by the host range of the retrovirus from which they were derived. To alter the host range of the vector particle, we developed a method to substitute the receptor-binding domain of the envelope protein of a retrovirus with an antigen-binding site of an antibody. To test whether such particles are competent for infection, we established a model system using an antigen-binding site of an antibody against the hapten dinitrophenol (DNP). Retroviral vector particles containing such chimeric envelope proteins were able to bind to and infect cells that were not infectable with wild-type virus after DNP was conjugated to the cell surface. They did not infect such cells without DNP conjugation. Control experiments with chimeric envelope proteins of ecotropic murine leukemia virus (eco-MLV) and spleen necrosis virus (SNV) indicate that the pathway of virus entry of scA-env-containing virus particles was different from that of wild-type virus.