Integrin-mediated vectors for gene transfer and therapy

Abstract

Gene therapy offers the possibility of new therapeutic strategies for diseases for which at present no cure exists. Current gene delivery systems, however, both viral and non-viral, have so far proven to be inadequate in one way or another and new efficient vector systems are required if gene therapy is to fulfill its clinical potential. The prospect of targeting integrins to improve vector efficiency is attractive since integrin-mediated internalization is exploited by bacterial and viral intracellular pathogens. Viral and synthetic vectors that incorporate peptide ligands for integrins have been exploited in the development of targeted vectors. This has generated enhanced efficiencies of transfection by synthetic vectors and transduction by adenoviral vectors, as well as extending the tropism of adenoviral vectors. The technology of phage display of random peptide libraries provides an approach to the selection of high-affinity peptide ligands, while the identification of integrin-binding motifs from natural protein ligands for integrins provides another source of peptides. Investigations into integrin receptors themselves, their activation and the signal transduction pathways they invoke may lead to further improvements in the design of integrin-targeted vectors and extensions to their potential applications in gene therapy.