AAV-mediated genetic interventions in the treatment of rare kidney disease: a narrative review

Abstract

Chronic kidney disease (CKD) is one of the leading causes of global morbidity and mortality. As CKD progresses, it can lead to end-stage renal disease (ESRD), which requires treatment such as dialysis or kidney transplantation. Rare kidney diseases, a distinct subset of CKD, are primarily caused by genetic mutations. Due to the limited basic and clinical research on rare kidney diseases, treatment options remain limited, and the risk of progression to ESRD is higher compared to that of common CKD. As a result, there is an urgent need to explore novel therapeutic strategies. Gene therapy, which involves the use of genetic material to prevent or treat diseases, offers new hope for CKD and rare kidney diseases, including both monogenic and complex kidney disorders. The goal of gene therapy is to restore or degrade the defective proteins that cause the disease, necessitating editing of disease-causing genes and effective gene delivery. However, due to the unique physiological characteristics of the kidney, such as high blood flow in renal vessels, the lack of effective targeting mechanisms for specific renal cells, and the presence of the glomerular basement membrane barrier, developing effective gene therapy is rather challenge. The lack of a kidney specific vector poses an additional challenge. Recently, emerging studies have shown encouraging results using recombinant adeno-associated virus (rAAV) vectors in the treatment of renal diseases. Several rAAV-based gene therapy products have entered clinical use. In this review, we summarize the current advancements in gene therapy mediated by rAAV vectors for rare kidney disease, particularly monogenic kidney diseases that lead to CKD, and discuss the future directions in this field. Clinical trial number : Not applicable.