Facilitation of retrovirus-mediated gene transfer into hematopoietic stem and progenitor cells and peripheral blood T-lymphocytes utilizing recombinant fibronectin fragments.

A transduction strategy has been developed, using fibronectin (FN)-assisted retroviral-mediated gene transfer, based on the observation that hematopoietic stem and progenitor cells bind to specific adhesion domains of fibronectin, via the integrins, very late antigen-4 (VLA-4)alpha 4 beta 1 and very late antigen-5 (VLA-5)alpha 5 beta 1. Retrovirus-mediated transduction on a recombinant FN fragment, FN CH-296, containing binding sites for VLA-4 and VLA-5, separated by type III repeats 12 to 14, makes it possible to efficiently target hematopoietic stem and progenitor cells and T-lymphocytes due to colocalization of target cells and retrovirus particles. These gene therapy strategies are applicable to the potential treatment of a variety of acquired and inherited immune disorders.