Jin L, Siritanaratkul N, Emery D W, Richard R E, Kaushansky K, Papayannopoulou T, Blau C A
Division of Hematology, Mailstop 357710, Health Sciences Building, University of Washington, Seattle WA 98195, USA.
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8093-7. doi: 10.1073/pnas.95.14.8093.
The ability to specifically target a mitogenic signal to a population of genetically modified primary cells would have potential applications both for gene and cell therapy. Toward this end, a gene encoding a fusion protein containing the FK506-binding protein FKBP12, fused to the 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 FK506, called FK1012, resulted in a marked proliferative expansion of marrow cells that was restricted to the genetically modified population. FK1012's proliferative effect was sustained and reversible. An apparent preference for differentiation along the megakaryocytic lineage was observed. This approach allows for the specific delivery of a mitogenic 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.
将有丝分裂信号特异性靶向一群基因改造的原代细胞的能力，在基因治疗和细胞治疗中都具有潜在应用价值。为此，将一个编码融合蛋白的基因导入原代小鼠骨髓细胞，该融合蛋白包含与血小板生成素受体（mpl）细胞内部分融合的FK506结合蛋白FKBP12。通过添加一种名为FK1012的二聚体形式药物FK506，使这种融合蛋白二聚化，导致骨髓细胞显著增殖扩增，且仅限于基因改造群体。FK1012的增殖作用是持续且可逆的。观察到明显倾向于沿巨核细胞系分化。这种方法能够将有丝分裂信号特异性传递给一群基因改造的原代细胞，可能在造血和受体生物学研究以及基因治疗和细胞治疗中具有应用价值。
