Nitroglycerin-responsive gene switch for the on-demand production of therapeutic proteins.

Gene therapies and cell therapies require precise, reversible and patient-friendly control over the production of therapeutic proteins. Here we present a fully human nitric-oxide-responsive gene-regulation system for the on-demand and localized release of therapeutic proteins through clinically licensed nitroglycerin patches. Designed for simplicity and robust human compatibility, the system incorporates human mitochondrial aldehyde dehydrogenase for converting nitroglycerin into nitric oxide, which then activates soluble guanylate cyclase to produce cyclic guanosine monophosphate, followed by protein kinase G to amplify the signal and to trigger target gene expression.