Therapeutics

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New everninomicin antibiotics including a potent bifunctional antibiotic natural product targeting two different and distant ribosomal sites are under development and can be readily produced using synthetic biology. Developing resistance to this bidentate antibiotic should be very difficult for pathogenic microorganisms.

Researchers at Vanderbilt have created a novel drug delivery system using two distinct T-cell populations that interact to promote engraftment and persistence in pre-clinical models, increasing the efficacy of T-cell therapies. Furthermore, "booster" treatments can be administered months after the first dose to produce an expansion of antigen specific T cells. These advantages result in longer-term therapeutic efficacy and could reduce the number of treatments required. This system also represents a viable self-renewing platform for the delivery of biologic drugs in patients who would otherwise require frequent administration.

Vascular inflammation caused by metabolic, autoimmune, and microbial insults mediates cardiovascular diseases that include hypertension and atherosclerosis (heart attacks, strokes), systemic lupus, and giant cell arteritis. An estimated 35 million Americans have hypercholesterolemia, contributing to 500,000 deaths underlying heart attacks and strokes. In these diseases, metabolic, autoimmune, and microbial insults continually challenge blood and vascular cells by triggering signaling to the nucleus mediated by BCL10. Genetic ablation of BCL10 rescues animals from atherosclerosis, aortic aneurysms, and fatty liver and insulin resistance due to overnutrition. Intracellular therapy with CP-CRADD is designed to extinguish BCL10-mediated noxious signals to avert vascular inflammation and its life-threatening complications including ruptured aneurysms in aorta and brain.

Probiotic supplements undergo significant water loss before consumption, killing many of their bacteria and rendering them less effective. Vanderbilt researchers have discovered a protein that protects against damage caused by desiccation and shown that this molecular shield can be added to probiotics to help them survive and colonize the gut. This platform technology can be broadly incorporated into new or existing supplements to make them more efficacious and even improve costs and distribution.