TARGETED EXPANSION OF GENETICALLY-MODIFIED BONE-MARROW CELLS

The ability to specifically target a mitogenic signal to a population of genetically modified primary cells would have potential application s both for gene and cell therapy. Toward this end, a gene encoding a f usion protein containing the FK506-binding protein FKBP12, fused to th e intracellular portion of the receptor for thrombopoietin (mpl), was introduced into primary murine bone marrow cells. Dimerization of this fusion protein through the addition of a dimeric form of the drug FK5 06, called FK1012, resulted in a marked proliferative expansion of mar row cells that was restricted to the genetically modified population, FK1012's proliferative effect was sustained and reversible. An apparen t preference for differentiation along the megakaryocytic lineage was observed, This approach allows for the specific delivery of a mitogeni c signal to a population of genetically modified primary cells and may have applications for studies in hematopoiesis and receptor biology, and for gene and cell therapy.