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使用CRISPR-Cas9技术进行基因编辑:对辅助生殖的潜在影响。

Gene editing using CRISPR-Cas9 technology: potential implications in assisted reproduction.

作者信息

Sahin Gizem Nur, Seli Emre

机构信息

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.

出版信息

Curr Opin Obstet Gynecol. 2025 Jun 1;37(3):141-148. doi: 10.1097/GCO.0000000000001022. Epub 2025 Apr 11.

Abstract

PURPOSE OF REVIEW

This article reviews the mechanisms, advancements, and potential implications of clustered regularly interspaced short palindromic repeats-associated (CRISPR-Cas) gene editing technology, with a specific focus on its applications in reproductive biology and assisted reproduction. It aims to explore the benefits and challenges of integrating this revolutionary technology into clinical and research settings.

RECENT FINDINGS

CRISPR-Cas9 is a transformative tool for precise genome editing, enabling targeted modifications through mechanisms like nonhomologous end joining (NHEJ) and homology-directed repair (HDR). Innovations such as Cas9 nickase and dCas9 systems have improved specificity and expanded applications, including gene activation, repression, and epigenetic modifications. In reproductive research, CRISPR has facilitated gene function studies, corrected genetic mutations in animal models, and demonstrated potential in addressing human infertility and hereditary disorders. Emerging applications include mitochondrial genome editing, population control of disease vectors via gene drives, and detailed analyses of epigenetic mechanisms.

SUMMARY

CRISPR-Cas9 technology has revolutionized genetic engineering by enabling precise genome modifications. This article discusses its mechanisms, focusing on the repair pathways (NHEJ and HDR) and methods to mitigate off-target effects. In reproductive biology, CRISPR has advanced our understanding of fertility genes, allowed corrections of hereditary mutations, and opened avenues for novel therapeutic strategies. While its clinical application in human-assisted reproduction faces ethical and safety challenges, ongoing innovations hold promise for broader biomedical applications.

摘要

综述目的

本文综述了成簇规律间隔短回文重复序列相关(CRISPR-Cas)基因编辑技术的机制、进展及潜在影响,特别关注其在生殖生物学和辅助生殖中的应用。旨在探讨将这一革命性技术整合到临床和研究环境中的益处与挑战。

最新发现

CRISPR-Cas9是一种用于精确基因组编辑的变革性工具,可通过非同源末端连接(NHEJ)和同源定向修复(HDR)等机制实现靶向修饰。诸如Cas9切口酶和dCas9系统等创新提高了特异性并拓展了应用范围,包括基因激活、抑制和表观遗传修饰。在生殖研究中,CRISPR促进了基因功能研究,纠正了动物模型中的基因突变,并在解决人类不孕和遗传性疾病方面显示出潜力。新兴应用包括线粒体基因组编辑、通过基因驱动控制病媒种群以及对表观遗传机制的详细分析。

总结

CRISPR-Cas9技术通过实现精确的基因组修饰彻底改变了基因工程。本文讨论了其机制,重点关注修复途径(NHEJ和HDR)以及减轻脱靶效应的方法。在生殖生物学中,CRISPR增进了我们对生育基因的理解,允许纠正遗传性突变,并为新的治疗策略开辟了道路。虽然其在人类辅助生殖中的临床应用面临伦理和安全挑战,但持续的创新有望实现更广泛的生物医学应用。

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