By creating chimeric proteins that contain the coding sequence for a conditional aggregation domain (CAD) fused to a proinsulin, a collaboration of industrial and acadmic scientists has come up with a protein delivery system that responds to exogenous treatment with a small molecule (Science 287, 826–830, 2000). When expressed in cells, the CAD fusions accumulate in the endoplasmic reticulum and form large aggregates. A small-molecule that binds to the CADs breaks up the aggregates, allowing the stored proteins to be secreted rapidly. To prove the concept, the team injected fibroblasts expressing a CAD-proinsulin fusion protein into the muscles of a mouse model of hyperglycemia. When the mice received the small-molecule orally, cells rapidly secreted therapeutic quantities of the protein and transiently corrected the animals' serum glucose levels. Senior author Tim Clackson, a researcher at ARIAD Gene Therapeutics (Cambridge, MA), says that “the applications go beyond insulin to any protein or peptide that needs to be delivered in short bursts. We are especially interested in delivery of endorphins for management of acute pain, where rapid delivery is essential.”