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宫内胎儿基因治疗:这是未来的方向吗?现在是未来了吗?

Intrauterine Fetal Gene Therapy: Is That the Future and Is That Future Now?

作者信息

Peddi Nikhil Chowdary, Marasandra Ramesh Harshita, Gude Sai Sravya, Gude Sai Sreeya, Vuppalapati Sravya

机构信息

Pediatrics, PES Institute of Medical Sciences and Research, Kuppam, IND.

Pediatrics, Kasturba Medical College, Mangalore, Mangalore, IND.

出版信息

Cureus. 2022 Feb 23;14(2):e22521. doi: 10.7759/cureus.22521. eCollection 2022 Feb.

Abstract

Researchers are looking into techniques to intervene sooner and earlier in the disease process thanks to advances in disease genetics, etiologies, and prenatal diagnosis. We conducted a literature search in PubMed-indexed journals to provide an overview of the evolution of gene therapy, rationale for prenatal gene therapy, uses and risks of gene therapy, and ethical issues following the usage of gene therapy. Recent animal research has revealed that transmitting genetic material to a growing fetus through viral and non-viral vectors is conceivable besides proving how gene-editing technology is achieved by various mechanisms that utilize zinc finger nucleases, TAL effector nucleases, and clustered short palindromic repeats-Cas9 complex. This review offers an overview of the current knowledge in the field of prenatal gene therapy, as well as potential future research avenues. In addition, it weighs the risks of prenatal gene therapy, such as oncogenesis, genetic mutation transfer from mother to child, and fetal disruption, against the expected benefits, such as preventing the development of severe early-onset illness symptoms, targeting previously inaccessible organs, and establishing tolerance to the therapeutic transgenic protein, all of which lead to permanent somatic gene correction. This review discusses the scientific, ethical, legal, and sociological implications of these groundbreaking genetic disease prevention techniques, as well as the parameters that must be satisfied for a future clinical application to be considered.

摘要

由于疾病遗传学、病因学和产前诊断方面的进展,研究人员正在探索在疾病进程中更早进行干预的技术。我们在PubMed索引的期刊上进行了文献检索,以概述基因治疗的发展、产前基因治疗的原理、基因治疗的用途和风险,以及基因治疗使用后的伦理问题。最近的动物研究表明,除了证明利用锌指核酸酶、转录激活因子样效应物核酸酶和成簇短回文重复序列-Cas9复合物的各种机制如何实现基因编辑技术外,通过病毒和非病毒载体将遗传物质传递给发育中的胎儿也是可行的。本综述概述了产前基因治疗领域的当前知识以及未来潜在的研究途径。此外,它权衡了产前基因治疗的风险,如肿瘤发生、基因突变从母亲传给孩子以及胎儿发育中断,与预期益处,如预防严重早发疾病症状的发展、靶向以前无法到达的器官以及建立对治疗性转基因蛋白的耐受性,所有这些都导致永久性体细胞基因校正。本综述讨论了这些开创性的遗传疾病预防技术的科学、伦理、法律和社会学意义,以及未来临床应用必须满足的参数。

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本文引用的文献

1
InUtero Gene Therapy: Progress and Challenges.子宫内基因治疗:进展与挑战。
Trends Mol Med. 2021 Aug;27(8):728-730. doi: 10.1016/j.molmed.2021.05.007. Epub 2021 Jun 24.
2
Delivery technologies for in utero gene therapy.子宫内基因治疗的递送技术。
Adv Drug Deliv Rev. 2021 Feb;169:51-62. doi: 10.1016/j.addr.2020.11.002. Epub 2020 Nov 9.
4
The Future of In Utero Gene Therapy.子宫内基因治疗的未来。
Mol Diagn Ther. 2020 Apr;24(2):135-142. doi: 10.1007/s40291-020-00445-y.
8
Fetal stem cell and gene therapy.胎儿干细胞与基因治疗。
Semin Fetal Neonatal Med. 2017 Dec;22(6):410-414. doi: 10.1016/j.siny.2017.05.003. Epub 2017 Jun 12.
9
Placenta-directed gene therapy for fetal growth restriction.胎盘靶向基因治疗胎儿生长受限。
Semin Fetal Neonatal Med. 2017 Dec;22(6):415-422. doi: 10.1016/j.siny.2017.04.005. Epub 2017 May 15.

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