Creating new specific ligand–receptor pairs for transgene regulation

The creation of specifically matched ligand–receptor pairs that are orthogonal to naturally present interacting pairs is essential for the development of small molecule-regulated gene expression systems for biotechnological applications. However, for many years this task has represented a significant challenge for synthetic chemists and protein engineers. Recently, Doyle and colleagues demonstrated that highly specific ligand–receptor pairs can be engineered in a rapid fashion by creating large libraries of protein variants and applying a selection scheme to identify variants with improved activation by the target synthetic ligand.