公开(公告)号：EP1442057B1

公开(公告)日：2012-06-13

申请号：EP02777580.8

申请日：2002-10-24

申请人： Creative Cell Kft.

发明人： NEMET, Katalin ,  VARADI, György ,  CERVENAK, Judit ,  UJHELLY, Olga ,  SARKADI, Balázs ,  VARADI, András ,  ÖZVEGY, Csilla

IPC分类号： C07K14/47 ,  C12N5/10 ,  A61K48/00 ,  C12N15/12 ,  C12N15/86 ,  C12N15/867

CPC分类号： C12N5/0647 ,  A61K48/00 ,  A61K2035/124 ,  C07K14/705 ,  C12N2510/00

摘要： Using an isolated nucleic acid comprising a sequence encoding a half transporter protein of the ABCG-family, in gene therapy methods, and in selecting somatic mammalian cells using at least one drug transportable by the transporter protein, is new. Independent claims are also included for: (1) a vector for gene transfer into a mammalian cell, comprising the nucleic acid; (2) selecting somatic mammalian cells using at least one drug transportable by the transporter protein; (3) somatic mammalian cells transformed by the vector; (4) an infectious virion obtainable from a viral vector; and (5) a pharmaceutical kit comprising the vector. ACTIVITY : Immunosuppressive. No biological data given. MECHANISM OF ACTION : Gene therapy; Hematopoietic cell protector. After retroviral transduction the cells were exposed to 5mM Mitoxanthrone (MX) selection for 3 days and induced for granulocyte differentiation by G-CSF, or plated directly in a colony forming assay and selected by MX in methylcellulose. Normal or mock transduced CD34+ cells did not show measurable MX extrusion capacity, but a significant increase in MX extrusion was seen in the ABCG2-G transduced progenitor cells, and this extrusion was further increased by MX selection of the transduced cells. When MX was used as a selection agent the mock transduced cells did not form colonies, while the MX selection decreased the number in the ABCG2-G transduced cells by about 50%. This reduction closely corresponds to the elimination of the cells not expressing ABCG2-G.