Mayo Clinic uses gene editing to reverse inherited kidney disease in preclinical study
Published in Diseases!.
ROCHESTER, Minn. — 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.
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.
“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.”
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.
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.
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.