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Colocalization of retrovirus and target cells on specific fibronectin fragments increases genetic transduction of mammalian cells | Nature Medicine
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Hematopoietic cells are important targets for genetic modification with retroviral vectors. Attempts at human gene therapy of stem cells have achieved limited success partly because of low gene transfer efficiency. Chymotryptic fragments of the extracellular matrix molecule fibronectin used during infection have been shown to increase transduction of human hematopoietic progenitor cells. Here, we demonstrate that this enhanced gene transfer into mammalian target cells is due to direct binding of retroviral particles to sequences within the fibronectin molecule. Transduction of mammalian cells, including murine long–term repopulating hematopoietic cells, is greatly enhanced when cells are adherent to chimeric fragments containing these retroviral binding sequences. In addition, colocalization of retrovirus and target cells on fibronectin peptides allows targeted transduction of specific cell types by exploiting unique ligand/receptor interactions.
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nature portfolio permissions reprints privacy policy advertising c-terminal heparin-binding domain nature med social media pediatric research nature 310 nature 318 nature 352 nature research hospital 2025 development lymphocyte-directed gene therapy research receptor phos-phatase cd45 chymotryptic carboxy-terminal fragments htlv-i-infected lymphocytes adoptive t-cell therapies korv-pseudotyped lentiviral vectors pediatric hematology/oncology personal data springerlink instant access long-term reconstitution retrovirus-mediated gene transfer matrix molecule interactions data protection xiang li xiao & david permissions autologous bone marrow long-term engraftment human gene therapy murine hematopoietic cells hematopoietic stem cells human hematopoietic cells efficient gene transfer specific cell types kimikazu hashino multipotent hematopoietic precursors human adenosine deaminase car-cell therapy human ngf receptor peripheral blood lymphocytes mouse bone marrow chemically modified heparins privacy adenosine deaminase deficiency carbonic anhydrase domain enhanced gene transfer
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