DNA-based delivery of incretin receptor agonists using MYO Technology leads to durable weight loss in a diet-induced obesity model.

Incretin receptor agonists (IRAs) have recently come to prominence as powerful weight and glucose control drugs and are approved for the treatment of type 2 diabetes (T2D) and obesity. Semaglutide and tirzepatide, currently the most widely prescribed within this class, are both potent molecules but have a short half-life, requiring weekly dosing. This requirement can negatively affect quality of life and the adherence to therapy, as well as create a significant financial burden for patients who may have a life-long need for treatment. The MYO Technology platform was developed to overcome these barriers. It consists of therapeutic-encoding plasmid DNA, and a proprietary medical device for intramuscular injection and in vivo electroporation of muscle cells. This leads to the uptake of injected DNA, expression of the therapeutic, and its secretion into peripheral circulation. Here, we demonstrate that MYO Technology-delivered IRAs are efficacious in promoting long-lasting weight and glucose control in mouse models of diet-induced obesity. Moreover, engineering the IRAs to facilitate blood-brain barrier penetration further enhances treatment efficacy, with benefits persisting beyond 1 year following a single administration. Together, these findings highlight MYO Technology's potential to transform standard of care by enabling long-lasting therapeutic effects with minimal dosing.