Major Rami M, Juengst Eric T
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Social Medicine and Center for Bioethics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Am J Hum Genet. 2025 Feb 6;112(2):201-214. doi: 10.1016/j.ajhg.2025.01.003. Epub 2025 Jan 28.
Neurodevelopmental diseases (NDDs) are notoriously difficult to treat because clinical symptoms stem from developmental processes that begin before birth. Prenatal gene editing could fill the treatment gap for NDDs by targeting and permanently correcting the genetic variants that underlie these pathogenic developmental processes. At the same time, there is a risk of unintended edits to the fetus or the pregnant person that could result in serious adverse consequences that are difficult, if not impossible, to undo. This raises ethical concerns that make the development of prenatal gene editing especially challenging. To date, there are no frameworks for considering the steps necessary for an ethical path forward for prenatal gene editing specifically. The 60-year history of in utero therapy has included the development of frameworks for other therapies that can provide starting points for addressing the unique issues of prenatal gene editing. We identified 12 themes from 17 ethical frameworks, literature, consensus statements, and government reports on prenatal interventions that could set precedents for prenatal gene editing interventions. In considering these alongside current criteria for postnatal gene therapies for NDDs, we discuss a path forward for prenatal gene editing interventions of NDDs.
神经发育疾病（NDDs） notoriously难以治疗，因为临床症状源于出生前就开始的发育过程。产前基因编辑可以通过靶向并永久纠正这些致病性发育过程背后的基因变异来填补NDDs的治疗空白。与此同时，存在对胎儿或孕妇进行意外编辑的风险，这可能导致严重的不良后果，即使不是不可能，也很难消除。这引发了伦理问题，使得产前基因编辑的发展尤其具有挑战性。迄今为止，尚无专门用于考虑产前基因编辑道德前进道路所需步骤的框架。子宫内治疗60年的历史包括为其他疗法制定框架，这些框架可为解决产前基因编辑的独特问题提供起点。我们从17个关于产前干预的伦理框架、文献、共识声明和政府报告中确定了12个主题，这些主题可为产前基因编辑干预树立先例。在将这些与当前NDDs产后基因治疗的标准一起考虑时，我们讨论了NDDs产前基因编辑干预的前进道路。
