Nature Medicine
2, 876 - 882 (1996)
doi:10.1038/nm0896-876
Colocalization of retrovirus and target cells on specific fibronectin fragments increases genetic transduction of mammalian cellsHelmut Hanenberg1, Xiang Li Xiao1, Dagmar Dilloo2, Kimikazu Hashino3, Ikunoshin Kato3
& David A. Williams1, 4, 5
1Section of Pediatric Hematology/Oncology, Herman B No. Wells Center for Pediatric Research, Riley Hospital for Children, Indiana University School of Medicine, 702
Barnhill Drive, Indianapolis, Indiana 46202-5225, USA
2St. Jude Children's Research Hospital, 332 North Lauderdale, P.O. Box 318, Memphis, Tennessee 38101-0318, USA
3Biotechnology Research Laboratories, Takara Shuzo Co., Ltd., Seta 3-4-1, Otsu, Shiga, 520-21, Japan
4Howard Hughes Medical Institute, Indiana University School of Medicine, 702 Barnhill Drive, Indianapolis, Indiana 46202-5225, USA
5Correspondence should be addressed to D.A.W. 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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