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不要忽视经基因组编辑的体细胞最终进入人类种系的可能性。

Do not overlook the possibility of genome-edited somatic cells ending up in the human germline.

作者信息

Chin Alexis Heng Boon, Sun Ningyu

机构信息

Singapore Fertility and IVF Consultancy Pvt Ltd., 531A Upper Cross Street, #04-95, Hong Lim Complex, Chinatown, 051531, Singapore.

Center for Reproductive Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

J Community Genet. 2024 Dec;15(6):749-752. doi: 10.1007/s12687-024-00741-8. Epub 2024 Oct 9.

Abstract

Most debates on human germline genome editing have limited discussions to just genetic modifications of sperm and eggs (gametes), their precursors within testicular or ovarian tissues, and preimplantation human embryos. What has largely been overlooked is that genome editing of somatic (non-reproductive) cells can also become heritable and can potentially be transmitted to future generations of human offspring under specific experimental conditions, due to the emergence of various new technology platforms. Most notably, the reprogramming of human somatic cells to a pluripotent "embryonic stem cell-like" state (i.e. induced pluripotent stem cells), has opened up the possibility that genome editing performed on human somatic cells can also be transmitted to future generations of human offspring when combined with other new technology platforms, such as in vitro gametogenesis, chimeric and synthetic embryos. Additionally, due to high levels of plasticity and extensive tissue remodeling within the human fetus during gestation, it is speculated that genome editing performed on fetal somatic cells intended for fetal gene therapy in utero may be unintentionally transmitted to the human germline. Hence, there should be strict regulatory oversight to ensure that any genome-edited somatic cell that ends up in the human germline via such aforementioned technology platforms does so in strict compliance with relevant legislation and ethical guidelines, especially that pertaining to safety issues with genome editing technology and its potential misuse in human enhancement and eugenics.

摘要

大多数关于人类生殖系基因组编辑的讨论都将范围局限于对精子、卵子(配子)、它们在睾丸或卵巢组织中的前体细胞以及植入前人类胚胎的基因改造。但很大程度上被忽视的是,由于各种新技术平台的出现,体细胞(非生殖细胞)的基因组编辑在特定实验条件下也可能具有遗传性,并有可能传递给人类后代。最值得注意的是,将人类体细胞重编程为多能的“胚胎干细胞样”状态(即诱导多能干细胞),这使得当与其他新技术平台(如体外配子发生、嵌合体和合成胚胎)结合时,对人类体细胞进行的基因组编辑也有可能传递给人类后代。此外,由于人类胎儿在妊娠期具有高度的可塑性和广泛的组织重塑,推测在子宫内进行胎儿基因治疗时对胎儿体细胞进行的基因组编辑可能会意外地传递给人类生殖系。因此,应该进行严格的监管,以确保任何通过上述技术平台最终进入人类生殖系的基因组编辑体细胞都严格遵守相关法律和伦理准则,特别是与基因组编辑技术安全问题及其在人类增强和优生学方面潜在滥用相关的准则。

相似文献

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Human Germline Genome Editing.人类种系基因组编辑
Am J Hum Genet. 2017 Aug 3;101(2):167-176. doi: 10.1016/j.ajhg.2017.06.012.
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Genome editing in pluripotent stem cells: research and therapeutic applications.多能干细胞中的基因组编辑:研究与治疗应用
Biochem Biophys Res Commun. 2016 May 6;473(3):665-74. doi: 10.1016/j.bbrc.2016.02.113. Epub 2016 Feb 27.

本文引用的文献

6
Fetal gene therapy.胎儿基因治疗。
J Inherit Metab Dis. 2024 Jan;47(1):192-210. doi: 10.1002/jimd.12659. Epub 2023 Aug 7.
7
Is chimerism associated with cancer across the tree of life?嵌合体与生命之树中的癌症有关吗?
PLoS One. 2023 Jun 29;18(6):e0287901. doi: 10.1371/journal.pone.0287901. eCollection 2023.
8
Mammalian in vitro gametogenesis.哺乳动物体外配子发生
Science. 2021 Oct;374(6563):eaaz6830. doi: 10.1126/science.aaz6830. Epub 2021 Oct 1.

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