COLOCALIZATION OF RETROVIRUS AND TARGET-CELLS ON SPECIFIC FIBRONECTINFRAGMENTS INCREASES GENETIC TRANSDUCTION OF MAMMALIAN-CELLS

Hematopoietic cells are important targets for genetic modification wit h retroviral vectors. Attempts at human gene therapy of stem cells hav e achieved limited success partly because of low gene transfer efficie ncy. Chymotryptic fragments of the extracellular matrix molecule fibro nectin used during infection have been shown to increase transduction of human hematopoietic progenitor cells. Here, we demonstrate that thi s enhanced gene transfer into mammalian target cells is due to direct binding of retroviral particles to sequences within the fibronectin mo lecule. Transduction of mammalian cells, including murine long-term re populating hematopoietic cells, is greatly enhanced when cells are adh erent to chimeric fragments containing these retroviral binding sequen ces. In addition, colocalization of retrovirus and target cells on fib ronectin peptides allows targeted transduction of specific cell types by exploiting unique ligand/receptor interactions.