Douar A M, Themis M, Coutelle C
Department of Biochemistry and Molecular Genetics, Imperial College, School of Medicine at St. Mary's, London, UK.
Mol Hum Reprod. 1996 Sep;2(9):633-41. doi: 10.1093/molehr/2.9.633.
Fetal somatic gene therapy is emerging as a new experimental approach, in particular to prevent irreversible perinatal disease manifestation for many inherited conditions. Early therapeutic gene application may also allow targeting of still expanding stem cell populations of organ or cell systems inaccessible later in life and help to avoid immune sensitization against the therapeutic vector system or transgene protein product. The progress in development of ultrasound scanning and embryofetoscopy over the last decade has made minimally invasive administration of therapeutic gene transfer vectors to the fetus in utero possible in principle. We review here the different considerations in choosing candidate diseases, the possible routes of administration and times in fetal development for application of a therapeutic gene and discuss the benefits and problems of present vector systems in this context. Given the many unknown aspects of fetal gene transfer, it is essential to extensively investigate this new approach to gene therapy in animal models for specific diseases, to improve on the technology of delivery and to assess efficacy of expression as well as the possible side effects before application to humans can be considered.
胎儿体细胞基因治疗正在成为一种新的实验方法，特别是用于预防许多遗传性疾病在围产期出现不可逆的病症表现。早期应用治疗性基因还可以针对生命后期难以触及的仍在不断扩展的器官或细胞系统干细胞群体，并有助于避免对治疗载体系统或转基因蛋白产物产生免疫致敏。过去十年中超声扫描和胚胎胎儿镜检查技术的发展，原则上已使在子宫内对胎儿进行治疗性基因转移载体的微创给药成为可能。我们在此回顾在选择候选疾病、治疗性基因应用的给药途径和胎儿发育时期等方面的不同考量，并讨论当前载体系统在此背景下的益处和问题。鉴于胎儿基因转移存在诸多未知方面，在考虑应用于人类之前，必须在针对特定疾病的动物模型中广泛研究这种新的基因治疗方法，改进递送技术，评估表达效果以及可能的副作用。
