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CRISPR-Cas9基因编辑:通过遗传性表观遗传修饰治愈遗传疾病。

CRISPR-Cas9 Gene Editing: Curing Genetic Diseases by Inherited Epigenetic Modifications.

作者信息

Kolanu Nikhil Deep

机构信息

China Medical University, Shenyang, China.

出版信息

Glob Med Genet. 2024 Mar 29;11(1):113-122. doi: 10.1055/s-0044-1785234. eCollection 2024 Jan.

Abstract

CRISPR-Cas9 gene editing, leveraging bacterial defense mechanisms, offers precise DNA modifications, holding promise in curing genetic diseases. This review critically assesses its potential, analyzing evidence on therapeutic applications, challenges, and future prospects. Examining diverse genetic disorders, it evaluates efficacy, safety, and limitations, emphasizing the need for a thorough understanding among medical professionals and researchers. Acknowledging its transformative impact, a systematic review is crucial for informed decision-making, responsible utilization, and guiding future research to unlock CRISPR-Cas9's full potential in realizing the cure for genetic diseases.  A comprehensive literature search across PubMed, Scopus, and the Web of Science identified studies applying CRISPR-Cas9 gene editing for genetic diseases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria covered in vitro and in vivo models targeting various genetic diseases with reported outcomes on disease modification or potential cure. Quality assessment revealed a generally moderate to high risk of bias. Heterogeneity prevented quantitative meta-analysis, prompting a narrative synthesis of findings.  CRISPR-Cas9 enables precise gene editing, correcting disease-causing mutations and offering hope for previously incurable genetic conditions. Leveraging inherited epigenetic modifications, it not only fixes mutations but also restores normal gene function and controls gene expression. The transformative potential of CRISPR-Cas9 holds promise for personalized treatments, improving therapeutic outcomes, but ethical considerations and safety concerns must be rigorously addressed to ensure responsible and safe application, especially in germline editing with potential long-term implications.

摘要

CRISPR-Cas9基因编辑技术利用细菌的防御机制,能够实现精确的DNA修饰,为治愈遗传疾病带来了希望。本综述对其潜力进行了批判性评估,分析了其在治疗应用、挑战及未来前景方面的证据。通过研究多种遗传疾病,评估了其疗效、安全性和局限性,强调了医学专业人员和研究人员深入了解的必要性。鉴于其变革性影响,进行系统综述对于做出明智决策、负责任地利用以及指导未来研究以释放CRISPR-Cas9在治愈遗传疾病方面的全部潜力至关重要。

通过在PubMed、Scopus和科学网进行全面的文献检索,按照系统评价和Meta分析的首选报告项目指南,确定了将CRISPR-Cas9基因编辑应用于遗传疾病的研究。纳入标准涵盖针对各种遗传疾病的体外和体内模型,且报告了对疾病修饰或潜在治愈的结果。质量评估显示,偏倚风险总体为中度到高度。异质性使得无法进行定量Meta分析,因此对研究结果进行了叙述性综合。

CRISPR-Cas9能够实现精确的基因编辑,纠正致病突变,为以前无法治愈的遗传疾病带来希望。利用遗传的表观遗传修饰,它不仅能修复突变,还能恢复正常基因功能并控制基因表达。CRISPR-Cas9的变革潜力为个性化治疗带来了希望,有望改善治疗效果,但必须严格解决伦理考量和安全问题,以确保负责任且安全地应用,尤其是在具有潜在长期影响的生殖系编辑中。

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