КАСАХАРА Нориюки (US),ШИСТЛ Роберт Х. (US),ХАКЕ Катрин (US),ШАКМАРИ Акош (AT),КРУКС Гай М. (US)
申请号：
RU2013151632/15
公开号：
RU2013151632A
申请日:
2012.04.20
申请国别(地区):
RU
年份:
2015
代理人:
摘要：
1. A method of hematopoietic stem cell transplantation (HSC) without radiation, comprising: (a) administering to a mammalian subject one or two doses of 2 to 10 mg / kg body weight of a purine base analogue selected from 6-thioguanine (6TG), 6-mercaptopurine (6-MP) or azathiopurine (AZA) as a preconditioning step； (b) transplanting donor hypoxanthine-guanine phosphoribosyltransferase (HPRT) donors to an HSC subject within 48-72 hours of the preconditioning step； (c) administering to the subject from about 1 up to 5 mg / kg purino analog of the base every 2-4 days for 2-8 weeks after the transplantation stage； characterized in that the method is carried out in the absence of pre-conditioning by irradiation. 2. The method according to claim 1, characterized in that the analogue of the purine base is 6TG. 3. The method according to claim 1, characterized in that the total dosage of 6TG administered to the subject does not exceed 105 mg. The method according to claim 1, characterized in that the total dosage of 6TG administered to the subject does not exceed 75 mg. The method according to claim 1, characterized in that the introduction in step (c) is performed every 3 days and for no more than four weeks after the transplantation step. The method according to claim 1, characterized in that more than 75% of genetically modified hematopoietic cells are observed in a subject. The method according to claim 1, characterized in that more than 95% of genetically modified hematopoietic cells are observed in a subject. The method according to claim 1, characterized in that HPRT-deficient HSCs for transplantation are made HPRT-deficient by introducing sequences encoding zinc finger nucleases (ZFN), effector nucleases like transcription activators (TALEN), matrix1. Способ трансплантации гемопоэтических стволовых клеток (HSC) без облучения, включающий:(a) введение млекопитающему субъекту одной или двух доз от 2 до 10 мг/кг массы тела аналога пуринового основания, выбранного из 6-ти
