In the ongoing battle against genetic disorders, MIT engineers have made a significant breakthrough, fine-tuning a gene therapy control circuit that could lead to more precise treatments for conditions like Fragile X syndrome and Friedreich’s ataxia. By harnessing a circuit capable of keeping gene expression within a desired range, they’re navigating around the dangers of over- or under-expression, which have plagued gene therapies past.
According to a report by MIT News, only a select few gene therapies have secured FDA approval, mainly because tailoring the expression of therapeutic genes has been a bit like hitting a moving target - something the MIT team's innovation may rectify. Their mechanism, called ComMAND, utilizes an incoherent feedforward loop (IFFL) where the activation of a therapeutic gene triggers a microRNA that keeps its expression in check.
“Other people have developed microRNA based incoherent feed forward loops, but what Kasey has done is put it all on a single transcript, and she showed that this gives the best possible control when you have variable delivery to cells,” Katie Galloway, the study's senior author, told MIT News. This simplification could prove to be a game-changer in genetic medicine.
The results thus far are promising. In human cell experiments, the ComMAND circuit maintained gene expression levels at roughly eight times what’s normally seen in healthy cells. Without ComMAND, gene expression soared beyond 50 times normal levels—posing significant safety concerns. While more research and potentially tuning is needed to perfect the dosages, the MIT team's headway offers new hope to those with genetic disorders, especially where patient numbers are small and funding scarce. "The challenge with a lot of those is they're also rare diseases, so you don't have large patient populations," Galloway explained in the MIT paper.
The success of these IFFL circuits could soon push gene therapy beyond its present limitations, ushering in a new era in the fight against single-gene disorders. With continued testing, including in animal models, the ComMAND circuit might soon command a pivotal role in delivering genetic therapies that are both safe and effective.
