Hope of safer cure for genetic diseases

Hope of safer cure for genetic diseases

"We have been able to overcome this problem", he says.

Diseases such as muscular dystrophy, kidney failure and diabetes could be treated more gently after scientists developed a tool that "switches on" genes rather than cutting them. Recently, some researchers have started using a "dead" form of Cas9 (dCas9), which can still target specific places in the genome, but no longer cuts DNA. These are coupled to the dCas9, along with the usual guide RNAs that help them locate the desired section of DNA. To work around that issue, the researchers split the protein into two, loading dCas9 into one virus and the switches and guide RNAs into another.

To test how well the new technique worked, the researchers experimented with mice that had three different diseases - kidney damage, type 1 diabetes and muscular dystrophy. In each case, they engineered their CRISPR/Cas9 system to boost the expression of an endogenous gene that could potentially reverse disease symptoms.

In the case of acute kidney damage, the Salk team programed CRISPR to overexpress a gene called klotho that can switch off in old age and cause poor renal function. In the diabetic mice, the targeted genes were those that promote the growth of insulin-producing cells, and after treatment, the mice were found to have lower blood glucose levels. For muscular dystrophy, the researchers expressed genes that have been previously shown to reverse disease symptoms, including one particularly large gene that can not easily be delivered via traditional virus-mediated gene therapies.

"We have been very satisfied with the results obtained in these mice which showed that by inducing the activation of certain genes, we can at the same time to observe physiological changes", says Fumiyuki Hatanaka, a scientist at the Salk Institute, one of the main co-authors of the study.

Izpisua Belmonte's team is now working to improve the specificity of their system and to apply it to more cell types and organs to treat a wider range of human diseases, as well as to rejuvenate specific organs and to reverse the aging process and age-related conditions such as hearing loss and macular degeneration.