Cell-specific targeting of Sindbis virus vectors displaying IgG-binding domains of protein A

• Published in: Nature biotechnology Vol. 15; no. 8; pp. 763 - 767
• Main Authors: Ohno, Kouichi, Sawai, Keisuke, lijima, Yasushi, Levin, Brandi, Meruelo, Daniel
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01.08.1997
• Subjects: Animals; Antibodies, Monoclonal; beta-Galactosidase - genetics; Binding Sites; Biological and medical sciences; Biotechnology; Cricetinae; Drug Delivery Systems; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Gene Transfer Techniques; Genetic engineering; Genetic technics; Genetic Vectors; HeLa Cells; Humans; Immunoglobulin G - metabolism; Membrane Glycoproteins - genetics; Methods. Procedures. Technologies; Mice; Recombinant Fusion Proteins - metabolism; Sindbis Virus; Staphylococcal Protein A - metabolism; Tumor Cells, Cultured; Vectors (cloning, transfer, expression). Insertion sequences and transposons; Viral Envelope Proteins - genetics; Virion - metabolism; Antigen presentation; Targeting; Togaviridae; IgG; Monoclonal antibody; Protein A; Sindbis virus; Virus; Specificity; Alphavirus; Coat protein; Target cell; Gene therapy; Vector
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt0897-763

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.