D'Ambrosio Viola, Huimei Chen, Vo Nicole, Siew Keith, Evans Rhys D R, Freedman Benjamin, Pesce Francesco
Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
Centre for Computational Biology (CCB) and Programme in Cardiovascular and Metabolic Disorders (CVMD), Duke-NUS Medical School, Singapore.
Clin Kidney J. 2025 Jul 31;18(9):sfaf246. doi: 10.1093/ckj/sfaf246. eCollection 2025 Sep.
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.
基因组编辑技术,特别是成簇规律间隔短回文重复序列(CRISPR)-Cas9,通过实现精确的基因修饰改变了生物医学研究。由于其高效性、成本效益和多功能性,CRISPR已广泛应用于从临床前模型的基础生物学研究到潜在治疗干预的各个研究阶段。在肾脏病学中,CRISPR是阐明肾脏疾病潜在分子机制和开发创新治疗方法的开创性工具。本综述综合了肾脏病学中基于CRISPR的基因编辑的最新进展,强调了其在遗传性肾脏疾病、多基因肾病和功能基因组学研究中的应用。利用CRISPR工程化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关键见解,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,碱基编辑和引导编辑的最新进展证明了在诸如阿尔波特综合征和常染色体显性多囊肾病等疾病中纠正致病突变的可行性。此外,CRISPR在异种移植中起着关键作用,基因编辑猪肾解决了关键的免疫和病毒学障碍。尽管前景广阔,但临床转化面临挑战,包括递送效率、脱靶效应和伦理考量。本综述概述了肾脏病学中基于CRISPR的基因编辑的现状和未来方向,强调了其在推进肾脏疾病研究和治疗方面的变革潜力。