Cell-specific targeting of Sindbis virus vectors displaying IgG-binding domains of protein A.
Sindbis virus can infect a broad range of insect and vertebrate cell types due to the widespread distribution of the cellular receptor for the virus. The development of Sindbis virus vectors that target specific cell types could have important implications for the design of gene therapy strategies. To achieve this goal we have designed and constructed Sindbis virus particles displaying the IgG-binding domain of protein A. The protein A-envelope chimeric Sindbis virus vector has minimal infectivities against baby hamster kidney and human cell lines. When used in conjunction with monoclonal antibodies that react with cell-surface antigens, however, the protein A-envelope chimeric virus was able to infect human cell lines with high efficiency. Infection rates were 90% or higher for human lymphoblastoid cells. A variety of cells could be targeted by changing the monoclonal antibody without generating a new recombinant virus.
Ohno
K
K
Department of Pathology, New York University Medical Center, NY 10016, USA.
Sawai
K
K
Iijima
Y
Y
Levin
B
B
Meruelo
D
D
D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D006224:Cricetinae; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012845:Sindbis Virus; D013205:Staphylococcal Protein A / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000235:genetics; D014771:Virion / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; D014759:Viral Envelope Proteins; C022012:glycoprotein E1, Sindbis virus; C064950:glycoprotein E2, Sindbis virus; D001616:beta-Galactosidase