Ligand-mediated retargeting of recombinant adenovirus for gene transfer invivo

The development of efficient and safe methods for in vivo gene transfer is central to the success of gene therapy. Recombinant adenoviral vectors, alt hough highly efficient, are limited by the host immune response, potential safety hazards due to obligatory cotransfer of Viral proteins, and their br oad tissue tropism. Here, we demonstrate in an animal model that host range and tissue tropism of a recombinant adenovirus from a distant species can be modified by complexing adenovirus with a cell-specific ligand. Thus, a r eplication-deficient lacZ recombinant human adenovirus, which naturally doe s not infect avian cells, allowed highly efficient and specific gene transf er to the liver of ducks in vivo when complexed with N-acefylglucosamine, a ligand for the chicken hepatic lectin. This combination of ligand-mediated receptor targeting with adenoviral uptake and intracellular processing of a given gene represents a novel approach to gene therapy of inherited and a cquired liver diseases.