Scientists have successfully used genome editing in the kidneys of mice for the first time.
The researchers were able to bypass a particular mutation that causes kidney damage, using both a cell and mouse model of the rare genetic disease, Joubert syndrome. The findings may have important implications for personalised treatment for patients in the future.
'This is the first time that gene editing within the kidney has been performed, even in a mouse model, as the design and delivery of the gene editing to the kidney has previously been thought to be too difficult,' said Professor John Sayer, from the Institute of Genetic Medicine at Newcastle University in the UK, who led the research.
Joubert syndrome is an inherited brain disorder that affects around one in 80,000 newborns and can cause varying degrees of physical and mental impairments, as well as visual problems. Kidney disease also occurs in up to one third of patients, most commonly in those with a faulty CEP290 gene. These patients may require dialysis or a kidney transplant during their teenage years or later.
In the current study, funded by Kidney Research UK, the researchers used urine samples from a 14-year-old patient with the faulty CEP290 gene, to grow kidney cells. They then performed a technique called 'exon-skipping' in which a strand of engineered DNA is used to cover up the faulty part of the gene. This means the mutated form of the gene is effectively bypassed when the DNA sequence is 'read' or transcribed by the cell.
As the technique had a positive effect in these cells, they next used genome editing in a mouse model of Joubert syndrome and in rodents suffering from kidney cysts and kidney failure. In both cases, they were able to halt the kidney disease.
The scientists now plan to test the technology in other mouse models and hope to start patient studies within the next three years.
'Our research is a major step forwards as we now know how we may be able to offer a therapy that corrects the gene mistake within kidney cells and prevent the development of genetic kidney disease,' Professor Sayer concluded.
The study was published in the Proceedings of the National Academy of Sciences.