UCL Institute for Women's Health, University College London, London, United Kingdom.
Head of Research Department of Maternal Fetal Medicine at the Institute for Women's Health, University College London, United Kingdom.
Semin Fetal Neonatal Med. 2017 Dec;22(6):415-422. doi: 10.1016/j.siny.2017.04.005. Epub 2017 May 15.
Fetal growth restriction (FGR) is a serious pregnancy complication affecting ∼8% of all pregnancies. There is no treatment to increase fetal growth in the uterus. Gene therapy presents a promising treatment strategy for FGR, with the use of adenoviral vectors encoding for proteins such as vascular endothelial growth factor (VEGF) and insulin-like growth factor demonstrating improvements in fetal growth, placental function, and neonatal outcome in preclinical studies. Safety assessments suggest no adverse risk to the mother or fetus for VEGF maternal gene therapy; a clinical trial is in development. This review assesses research into placenta-directed gene therapy for FGR, investigating the use of transgenes and vectors, their route of administration in obstetrics, and the steps that will be needed to take this treatment modality into the clinic.
胎儿生长受限(FGR)是一种严重的妊娠并发症,影响所有妊娠的约 8%。目前没有治疗方法可以增加子宫内胎儿的生长。基因治疗为 FGR 提供了一种很有前途的治疗策略,使用腺病毒载体编码血管内皮生长因子(VEGF)和胰岛素样生长因子等蛋白已在临床前研究中显示出改善胎儿生长、胎盘功能和新生儿结局的作用。安全性评估表明,VEGF 母系基因治疗对母亲或胎儿没有不良风险;一项临床试验正在进行中。本综述评估了针对 FGR 的胎盘定向基因治疗研究,探讨了转染基因和载体的应用、在产科中的给药途径,以及将这种治疗模式推向临床所需的步骤。