Very few gene therapy treatments have been approved by the FDA. One of the challenges to developing these treatments has been achieving control over how much the new gene is expressed in cells — too little and it won’t succeed, too much and it could cause serious side effects.
To demonstrate this system, the researchers designed ComMAND circuits that could deliver the gene FXN, which is mutated in Friedreich’s ataxia — a disorder that affects the heart and nervous system. They also delivered the gene Fmr1, whose dysfunction causes fragile X syndrome. In tests in human cells, they showed that they could tune gene expression levels to about eight times the levels normally seen in healthy cells.
Without ComMAND, gene expression was more than 50 times the normal level, which could pose safety risks. Further tests in animal models would be needed to determine the optimal levels, the researchers say.
