ROCHESTER, Minn. \u2014 Mayo Clinic researchers have developed a promising gene-editing therapy that directly corrects a genetic mutation responsible for autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disorder.<\/p>\n
A single treatment of the gene therapy slowed kidney cyst growth, improved heart and liver health, and extended survival in preclinical models of ADPKD. The findings were published in Nature Communications.<\/p>\n
“This is the first time we’ve been able to show that base editing can effectively and safely correct a disease-causing mutation in the kidney in a complex biological system,” says Xiaogang Li, Ph.D., nephrology researcher and senior author of the study. “Instead of managing symptoms, this strategy goes after the underlying cause of the disease.”<\/p>\n
ADPKD affects an estimated 12 million people worldwide. The disease is caused primarily by mutations in the PKD1 or PKD2 genes and leads to the progressive growth of fluid-filled cysts in the kidneys, often resulting in kidney failure. Many patients also develop complications outside the kidneys, including heart enlargement and liver disease.<\/p>\n
Current treatments can slow disease progression but do not address its genetic root. The new approach, developed by Mayo Clinic investigators, uses a form of CRISPR-based gene editing known as base editing to precisely correct a single-letter DNA mutation in the PKD1 gene.<\/p>\n
In the study, researchers engineered two versions of a base editor: one designed to work broadly across multiple organs and another tailored specifically to kidney cells. Delivered using adeno-associated virus (AAV) vectors, a single dose of the therapy corrected the PKD1 mutation in a significant proportion of cells in kidney tissue and, depending on the editor used, in the heart and liver as well.<\/p>\n