The use of gene therapy tools in reproductive immunology research.
The use of gene therapy tools in reproductive immunology research.
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基因治疗工具在生殖免疫学研究中的应用。
DOI：
10.2174/156652305774329276
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发表时间：
2005
影响因子：
3.6
通讯作者：
H. Volk
中科院分区：
文献类型：
--
作者：
A. Zenclussen;M. Zenclussen;T. Ritter;H. Volk
哺乳动物怀孕是一个复杂的现象，允许母体免疫系统支持其异体胎儿，同时仍然有效地对抗病原体。基因治疗方法有可能治疗毁灭性的遗传性疾病，而传统疗法对这些疾病几乎没有希望。在生殖医学方面，迄今为止只进行了纠正子宫内基因缺陷的实验试验。利用基因疗法提高怀孕成功率或避免与怀孕有关的疾病，如流产或先兆子痫，仍然是一个非常遥远的目标，具有尚未解决的道德和伦理问题。然而，基因治疗可能有助于确定几个基因在支持胎儿生长和/或避免其排斥实验中的作用，并可能进一步帮助确定新的干预目标。避免胎儿排斥的基因治疗策略可能包括细胞保护分子在胎儿-胎盘界面的局部转移和表达。此外，对免疫细胞进行体外基因修饰以诱导耐受性是一种新颖而诱人的方法。在这方面，我们通过用编码HO-1的腺病毒治疗流产动物，证实了细胞保护和免疫调节分子血红素加氧酶-1 （HO-1）的作用。由于控制载体的单一应用不会对妊娠结果产生有害影响，我们建议使用实验性基因治疗来揭示导致妊娠成功的分子和细胞途径。
Mammalian pregnancy is a complex phenomenon allowing the maternal immune system to support its allogeneic fetus, while still being effective against pathogens. Gene therapy approaches have the potential to treat devastating inherited diseases for which there is a little hope of finding a conventional cure. In reproductive medicine, experimental trials have been made so far only for correcting gene defects in utero. The use of gene therapy for improving pregnancy-rate success or avoiding pregnancy-related diseases i.e. miscarriage or pre-eclampsia, remains a very distant goal with unresolved moral and ethical aspects. However, gene therapy may help determining the role of several genes in supporting fetal growth and/or avoiding its rejection experimentally and might further help to identify new targets of intervention. Gene therapy strategies to avoid fetal rejection may include the transfer and expression of cyto-protective molecules locally at the fetal-placental interface. In addition, the ex-vivo genetic modification of immune cells for tolerance induction is a novel and tempting approach. In this regard, we have confirmed the role of the cyto-protective and immunomodulatory molecule Heme Oxygenase-1 (HO-1), by treating animals undergoing abortion with an adenovirus coding for HO-1. Since the sole application of a control vector did not provoke deleterious effects in pregnancy outcome, we propose the use of experimental gene therapy for unveiling molecular and cellular pathways leading to pregnancy success.