In-vivo gene transfer to the uterine endometrium

In-vivo gene transfer to the uterine endometrium
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DOI:
10.1093/humrep/12.1.17
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发表时间:
1997-01-01
期刊:
影响因子:
6.1
通讯作者:
Smith, SK
Smith, SK
中科院分区:
医学1区
文献类型:
--
作者:
CharnockJones, DS;Sharkey, AM;Smith, SK

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生殖生物学的治疗干预很大程度上依赖于类固醇和抗类固醇,它们的作用是调节靶组织中的基因表达,虽然它们的使用改变了妇女的生活,但避孕技术方面的概念进展很少,没有确定改善人类植入的方法,也没有开发出治疗良性妇科的新策略。作为在子宫内实现这一目标的第一步,我们使用报告基因构建体在体内转染小鼠子宫内膜和体外转染人子宫内膜上皮细胞,我们在假妊娠的第2天将dna -脂质体复合物注射到小鼠的子宫腔内,并在2天后检测报告基因的活性。脂质体为2,3-二聚氧氧基- n -[2(精胺羧基)乙基]- n - n -二甲基-1-丙胺三氟乙酸酯和二聚磷脂酰乙醇胺的3:1 (w/w)混合物,用类似的dna -脂质体复合物在体外成功转染了新鲜分离的人子宫内膜上皮细胞,这些数据表明子宫内膜基因转移可能对人类有效,这可能导致新的治疗药物的开发,包括避孕药。改善妇女健康状况。
Therapeutic interventions in reproductive biology have relied largely on steroids and antisteroids which act to regulate gene expression in target tissues, Whilst their use has transformed women's lives, few conceptual advances have been made in contraceptive technology, no means identified to improve human implantation and no new strategies developed for the treatment of benign gynaecology. A novel alternative is direct gene transfer to the organ of interest, As a first step to achieving this goal in the uterus, we used reporter gene constructs to transfect mouse endometrium in vivo and human endometrial epithelial cells in vitro, We injected DNA-liposome complexes into the uterine lumen of mice on day 2 of pseudopregnancy and detected reporter gene activity 2 days later, The liposomes used were a 3:1 (w/w) mixture of 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N-N-dimethyl-1-propanaminium trifluoroacetate and dioleoylphosphatidyl ethanolamine, Freshly isolated human endometrial epithelial cells were successfully transfected in vitro with similar DNA-liposome complexes, These data suggest that endometrial gene transfer may be effective in humans, This may lead to the development of new therapeutic agents, including contraceptives, for the improvement of women's health.