The researchers used gene editing and 3-D human cell models known as organoids to study the genetics of PKD. Organoids are 3-D structures that mimic the features of an organ’s structure and function. They are grown from induced pluripotent stem cells, which can become any kind of cell in the body. The researchers used a gene editing technique called base editing to create mutations in certain locations on the *PKD1* and *PKD2* genes in human stem cells. They focused on four types of mutations in these genes that are known to cause PKD by disrupting the production of polycystin, a protein crucial for kidney function.
The study found that organoids with two defective gene copies always produced cysts, while those that carried one good gene copy and one defective gene copy did not. This suggests that having a single normal copy of the defective gene could prevent the formation of dangerous cysts in PKD. The researchers also discovered that a type of drug, known as a glycoside, can sidestep the effects of the defective gene in PKD, potentially setting the stage for new therapeutic approaches to treating the disease.