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 1gG, 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. (C) 2002 Elsevier Science B.V. All rights reserved.