Protein drugs have become a standard treatment for an increasing number of severe diseases. However, the complex and labor-intensive production process makes protein drugs very costly. Therefore, therapeutic proteins cause a considerable burden to our social security system. A possible solution is to enable patients to produce their own therapeutic proteins. This can be achieved by using synthetic messenger RNAs (mRNAs). In our body millions of mRNAs, each bearing a unique code, are produced and translated into proteins. Nowadays researchers can make synthetic mRNAs that encode for any desired protein. Moreover, advanced technologies have been developed to deliver such synthetic mRNAs to animals and humans. However, one bottleneck is the lack of control over the timing, duration and dose of the produced therapeutic proteins after in vivo administration of synthetic mRNAs. We recently managed to engineer synthetic mRNAs whose translation can be controlled by a small molecule (=regulator). In this project we want to evaluate for the first time such regulatable mRNAs in vivo. Several regulatable mRNAs will be created and the best in vivo delivery approach will be identified. Subsequently, the expression profile after repeated administration and the capacity of the regulator to reversibly modulate the translation in a dose dependent manner will be studied. Finally, one selected regulatable mRNA encoding a therapeutic protein will be investigated in a murine arthritis model.