Injectable protease-operated depots of glucagon-like peptide-1 provide extended and tunable glucose control Academic Article uri icon


  • Peptide drugs are an exciting class of pharmaceuticals increasingly used for the treatment of a variety of diseases; however, their main drawback is a short half-life, which dictates multiple and frequent injections and an undesirable “peak-and-valley” pharmacokinetic profile, which can cause undesirable side-effects. Synthetic prolonged release formulations can provide extended release of biologically active native peptide, but their synthetic nature can be an obstacle to production and utilization. Motivated by these limitations, we have developed a new and entirely genetically encoded peptide delivery system—Protease Operated Depots (PODs)—to provide sustained and tunable release of a peptide drug from an injectable sc depot. We demonstrate proof-of-concept of PODs, by fusion of protease cleavable oligomers of glucagon-like peptide-1, a type-2 diabetes drug, and a thermally …

publication date

  • February 19, 2013