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.
Herman B Wells Center for Pediatric Research, Riley Hospital for Children, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202-5525, USA. kpollok@iupui.edu
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Williams
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011323:Primates; D017469:Receptors, Fibronectin / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014161:Transduction, Genetic
D018952:Antigens, CD34; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D010446:Peptide Fragments; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins