CRISPR-Cas9 as a Targeted Therapeutic Strategy for Primary Hyperoxaluria: A New Frontier in Gene-Based Nephrology

Primary hyperoxaluria (PH), most commonly caused by mutations in the AGXT gene (type 1), is a rare inherited metabolic disorder leading to oxalate overproduction and progressive renal damage. Current treatments, including pyridoxine supplementation and RNA interference therapies, are supportive but not curative, with liver–kidney transplantation remaining the definitive option. CRISPR-Cas9 gene-editing technology offers a potential one-time curative solution by directly correcting pathogenic mutations or silencing disease-related genes. Recent preclinical studies and early clinical trials, such as those investigating YOLT-203, have shown promising reductions in urinary oxalate with minimal toxicity. However, challenges related to long-term safety, delivery, cost, and ethical concerns must be addressed. With further research and responsible innovation, CRISPR-Cas9 could revolutionize the treatment landscape of primary hyperoxaluria.