Hematopoietic stem cells are important targets for genetic modification with retroviral vectors. However, attempts to establish protocols applicable for human gene therapy of stem cells have achieved limited success due in part to low gene transfer efficiency. We have shown that exposure of target cells to chymotryptic or recombinant fragments of the extracellular matrix molecule fibronectin during the transduction protocol increases retrovirusmediated gene transfer into hematopoietic stem and progenitor cells without the need for co-culture on the producer cells. The mechanism of this enhanced gene transfer into target cells is at least partly due to direct binding of retroviral particles to sequences within the fibronectin molecule. Transduction of mammalian cells is greatly enhanced when cells are adherent to chimeric fibronectin fragments which contain binding sites for either VLA-4 or VLA-5 integrins expressed on various target cells in combination with these retroviral binding sequences. Furthermore, we suggest that co-localization of retrovirus and cells on fibronectin peptides should allow targeted transduction of specific cell types by exploiting unique ligang/ receptor interactions. This mechanism may have implications not only for retroviral vectors, but also for natural retroviral infection.
|Original language||English (US)|
|Number of pages||1|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
- Cancer Research