Final Report Summary - PRONET (ProNet - Prosthetic Transgene Networks for the Treatment of Metabolic Disorders)
The direct connection between sensor (input) and effector (output) capacities known as closed-loop control enables the implanted designer cells to detect and diagnose pathologic levels of critical disease-associated metabolites at an early asymptomatic stage and correct the deficiency in real time. At any point in time, closed-loop control ensures that input and output is dynamically coordinated. This ensures that when disease metabolite (e.g. blood fat or glucose levels) levels are high, therapeutic protein levels are high (e.g. appetite-suppressing hormone or insulin). Closed-loop control circuits are not only activated and constantly adjusted to disease metabolite input, they also automatically shut down as the therapeutic effector protein corrects the disease disease and corresponding metabolites decrease.
Designer cells containing closed-looped gene circuits are microencapsulated and implanted into the body. Protected by the host immune system, the designer cells automatically connect to the bloodstream, which enables them to sense and correct a specific disease. Prosthetic networks have been designed and successfully validated in proof-of-concept studies for the treatment of the metabolic syndrome, hypertension, obesity, diabetic ketoacidosis, insulin resistance, type-1 diabetes, type-2 diabetes, psoriasis, Grave's disease, Pseudomonas aeruginosa infections, multidrug-resistant Staphylococcus aureus (MRSA) infections, allergies and chronic pain.
Extending the century-old concept of prostheses to the molecular level has paved the way for new opportunities of cell-based therapies to treat and cure the most prominent diseases.