Adaptable modification of adenoviral tropism using a bifunctional ligand protein.
In order to target recombinant adenovirus (AdV), we have developed a new strategy using a fusion ligand protein comprising coxsackievirus/adenovirus receptor (CAR), and the antibody Fc-binding domain from protein A in vitro testing with this ligand shows that it blocks viral gene transduction and, when coupled with anti-ICAM-1 IgG, redirects AdV to endothelial cells that are induced to express ICAM-1. Because the protein A Fc-binding domain will bind to any immunoglobulin, the current strategy can be adapted to target a wide variety of tissues or cells as long as an antibody species that recognizes a membrane marker on target tissue or cell is present. This concept may be further expanded to other viruses that employ peptide receptors. These membrane receptors can be fused to the Fc-binding domain to create a variety of bifunctional ligands for targeting recombinant viruses in gene therapy.
Li
Yibing
Y
Rainbow Therapeutic Company, 145B Lomita Street, San Francisco, CA 94122, USA. ybli@sbcglobal.net
Yao
Xiao Ming
XM
Hong-Brown
Ly
L
Massa
Stephen M
SM
D000256:Adenoviridae / Q000235:genetics / Q000472:pathogenicity*; D000818:Animals; D002478:Cells, Cultured; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004730:Endothelium, Vascular; D005818:Genetic Engineering / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008164:Luminescent Proteins; D051379:Mice; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D007074:Immunoglobulin G; D008024:Ligands; D008164:Luminescent Proteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins