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

ABSTRACT 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.