CRISPR和基因编辑治疗肾病:进展如何?

IF 4.6 2区 医学 Q1 UROLOGY & NEPHROLOGY
Clinical Kidney Journal Pub Date : 2025-07-31 eCollection Date: 2025-09-01 DOI:10.1093/ckj/sfaf246
Viola D'Ambrosio, Chen Huimei, Nicole Vo, Keith Siew, Rhys D R Evans, Benjamin Freedman, Francesco Pesce
{"title":"CRISPR和基因编辑治疗肾病:进展如何?","authors":"Viola D'Ambrosio, Chen Huimei, Nicole Vo, Keith Siew, Rhys D R Evans, Benjamin Freedman, Francesco Pesce","doi":"10.1093/ckj/sfaf246","DOIUrl":null,"url":null,"abstract":"<p><p>Genome editing technologies, particularly clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, have transformed biomedical research by enabling precise genetic modifications. Due to its efficiency, cost-effectiveness and versatility, CRISPR has been widely applied across various stages of research, from fundamental biological investigations in preclinical models to potential therapeutic interventions. In nephrology, CRISPR represents a groundbreaking tool for elucidating the molecular mechanisms underlying kidney diseases and developing innovative therapeutic approaches. This review synthesizes the latest advancements in CRISPR-based gene editing within nephrology, highlighting its applications in genetic kidney disorders, polygenic nephropathies and functional genomic studies. Preclinical studies utilizing CRISPR-engineered kidney organoids and animal models have provided crucial insights into disease pathophysiology, offering platforms for drug discovery and precision medicine. Additionally, CRISPR-based functional screens have identified novel disease-associated pathways, particularly in diabetic nephropathy and glomerular disorders. Beyond experimental research, the therapeutic potential of CRISPR in nephrology is emerging, with recent advances in base editing and prime editing demonstrating the feasibility of correcting pathogenic mutations in conditions such as Alport syndrome and autosomal dominant polycystic kidney disease. Moreover, CRISPR plays a pivotal role in xenotransplantation, with gene-edited porcine kidneys addressing key immunological and virological barriers. Despite its promise, clinical translation faces challenges, including delivery efficiency, off-target effects and ethical considerations. This review provides an overview of the current state and future directions of CRISPR-based gene editing in nephrology, underscoring its transformative potential in advancing kidney disease research and therapeutics.</p>","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":"18 9","pages":"sfaf246"},"PeriodicalIF":4.6000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415518/pdf/","citationCount":"0","resultStr":"{\"title\":\"CRISPR and gene editing for kidney diseases: where are we?\",\"authors\":\"Viola D'Ambrosio, Chen Huimei, Nicole Vo, Keith Siew, Rhys D R Evans, Benjamin Freedman, Francesco Pesce\",\"doi\":\"10.1093/ckj/sfaf246\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Genome editing technologies, particularly clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, have transformed biomedical research by enabling precise genetic modifications. Due to its efficiency, cost-effectiveness and versatility, CRISPR has been widely applied across various stages of research, from fundamental biological investigations in preclinical models to potential therapeutic interventions. In nephrology, CRISPR represents a groundbreaking tool for elucidating the molecular mechanisms underlying kidney diseases and developing innovative therapeutic approaches. This review synthesizes the latest advancements in CRISPR-based gene editing within nephrology, highlighting its applications in genetic kidney disorders, polygenic nephropathies and functional genomic studies. Preclinical studies utilizing CRISPR-engineered kidney organoids and animal models have provided crucial insights into disease pathophysiology, offering platforms for drug discovery and precision medicine. Additionally, CRISPR-based functional screens have identified novel disease-associated pathways, particularly in diabetic nephropathy and glomerular disorders. Beyond experimental research, the therapeutic potential of CRISPR in nephrology is emerging, with recent advances in base editing and prime editing demonstrating the feasibility of correcting pathogenic mutations in conditions such as Alport syndrome and autosomal dominant polycystic kidney disease. Moreover, CRISPR plays a pivotal role in xenotransplantation, with gene-edited porcine kidneys addressing key immunological and virological barriers. Despite its promise, clinical translation faces challenges, including delivery efficiency, off-target effects and ethical considerations. This review provides an overview of the current state and future directions of CRISPR-based gene editing in nephrology, underscoring its transformative potential in advancing kidney disease research and therapeutics.</p>\",\"PeriodicalId\":10435,\"journal\":{\"name\":\"Clinical Kidney Journal\",\"volume\":\"18 9\",\"pages\":\"sfaf246\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415518/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Kidney Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ckj/sfaf246\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Kidney Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ckj/sfaf246","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

基因组编辑技术,特别是聚集规律间隔短回文重复序列(CRISPR -Cas9),通过实现精确的基因修饰,已经改变了生物医学研究。由于其效率,成本效益和多功能性,CRISPR已广泛应用于各个研究阶段,从临床前模型的基础生物学研究到潜在的治疗干预。在肾脏病学中,CRISPR代表了一种突破性的工具,用于阐明肾脏疾病的分子机制和开发创新的治疗方法。本文综述了基于crispr的基因编辑在肾病学中的最新进展,重点介绍了其在遗传性肾病、多基因肾病和功能基因组研究中的应用。利用crispr工程肾脏类器官和动物模型的临床前研究为疾病病理生理学提供了重要见解,为药物发现和精准医学提供了平台。此外,基于crispr的功能筛选已经确定了新的疾病相关途径,特别是在糖尿病肾病和肾小球疾病中。除了实验研究,CRISPR在肾脏病学中的治疗潜力正在显现,最近在碱基编辑和启动体编辑方面的进展证明了纠正Alport综合征和常染色体显性多囊肾病等疾病的致病突变的可行性。此外,CRISPR在异种移植中发挥着关键作用,基因编辑的猪肾脏解决了关键的免疫和病毒学障碍。尽管前景光明,但临床翻译面临着递送效率、脱靶效应和伦理考虑等挑战。这篇综述概述了基于crispr的基因编辑在肾病学中的现状和未来方向,强调了其在推进肾脏疾病研究和治疗方面的变革潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

CRISPR and gene editing for kidney diseases: where are we?

CRISPR and gene editing for kidney diseases: where are we?

CRISPR and gene editing for kidney diseases: where are we?

Genome editing technologies, particularly clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, have transformed biomedical research by enabling precise genetic modifications. Due to its efficiency, cost-effectiveness and versatility, CRISPR has been widely applied across various stages of research, from fundamental biological investigations in preclinical models to potential therapeutic interventions. In nephrology, CRISPR represents a groundbreaking tool for elucidating the molecular mechanisms underlying kidney diseases and developing innovative therapeutic approaches. This review synthesizes the latest advancements in CRISPR-based gene editing within nephrology, highlighting its applications in genetic kidney disorders, polygenic nephropathies and functional genomic studies. Preclinical studies utilizing CRISPR-engineered kidney organoids and animal models have provided crucial insights into disease pathophysiology, offering platforms for drug discovery and precision medicine. Additionally, CRISPR-based functional screens have identified novel disease-associated pathways, particularly in diabetic nephropathy and glomerular disorders. Beyond experimental research, the therapeutic potential of CRISPR in nephrology is emerging, with recent advances in base editing and prime editing demonstrating the feasibility of correcting pathogenic mutations in conditions such as Alport syndrome and autosomal dominant polycystic kidney disease. Moreover, CRISPR plays a pivotal role in xenotransplantation, with gene-edited porcine kidneys addressing key immunological and virological barriers. Despite its promise, clinical translation faces challenges, including delivery efficiency, off-target effects and ethical considerations. This review provides an overview of the current state and future directions of CRISPR-based gene editing in nephrology, underscoring its transformative potential in advancing kidney disease research and therapeutics.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Clinical Kidney Journal
Clinical Kidney Journal Medicine-Transplantation
CiteScore
6.70
自引率
10.90%
发文量
242
审稿时长
8 weeks
期刊介绍: About the Journal Clinical Kidney Journal: Clinical and Translational Nephrology (ckj), an official journal of the ERA-EDTA (European Renal Association-European Dialysis and Transplant Association), is a fully open access, online only journal publishing bimonthly. The journal is an essential educational and training resource integrating clinical, translational and educational research into clinical practice. ckj aims to contribute to a translational research culture among nephrologists and kidney pathologists that helps close the gap between basic researchers and practicing clinicians and promote sorely needed innovation in the Nephrology field. All research articles in this journal have undergone peer review.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信