Small molecule therapeutics dominated medical interventions in the twentieth century and remain essential today. Yet, it is becoming apparent that small-molecule drugs are not ideally suited to treat all diseases. In many cases the most effective treatment may be a biological macromolecule such as a therapeutic protein. One can point to many successes using natural as well as engineered proteins. Despite the clear utility of manufactured proteins as therapeutics, it remains incredibly expensive to develop, manufacture, and deliver these agents, effectively limiting their impact on human health, especially in the developing world. Gene therapy (treatment using DNA-encoded therapeutic proteins) is attractive for a variety of reasons. However, the current lack of safe and effective methods to regulate the expression and biological activity of gene-based therapeutics seriously limits the number and types of diseases that are under investigation. Recent success using adoptive cell therapy to treat certain blood cancers using a patients' modified immune cells represents an important step in the right direction. New regulation methods that are safe, effective, and genetically concise will dramatically expand the universe of diseases that can be targeted for treatment through gene therapy, thus opening new frontiers for treating human diseases that cannot be addressed using existing methods. The focus of this talk will be the development of novel regulation technologies based on conditional protein stability.