The Kath-Schorr lab develops artificial nucleic acids (DNA, RNA) from synthetic nucleic acid building blocks that perform novel functions and can, besides recognition of biological relevant target molecules, also possess catalytic activity. Our projects combine classical organic synthesis to produce complex unnatural nucleotide building blocks and to develop new functional nucleic acids with approaches from chemical biology to answer biological questions about specific RNA folding and function. We further study the influence on natural and artificial nucleotide modifications on RNA folding and stability to develop novel approaches for therapeutic applications of nucleic acids.
RNA therapeutics, in this case mRNA and siRNA, have established themselves in medicine and are becoming increasingly important. The stability of the applied RNA therapeutics in humans is an essential criterion for their pharmacological efficacy. Moreover, a better understanding of the fine control and regulation of protein expression of in vitro transcribed mRNA is essential for the further development of mRNA therapeutics.
In our projects we aim to further expand and apply our developed techniques to study specific coding and non-coding RNA molecules. Besides structural investigations on RNA in vitro, we aim to investigate in the biological function of specific non-coding RNAs in cells using our novel chemical tools for site-specific RNA labeling, as well as develop new approaches for nucleic acid therapeutics by chemical modification of nucleic acid building blocks.
L. Bornewasser C. Domnick and S. Kath-Schorr* "Stronger together for in-cell translation: natural and unnatural base modified mRNA" Chemical Science.2022, 13, 4753-4761 (*front cover, *Chem. Sci. hot article collection).
L. Bornewasser and S. Kath-Schorr* "Preparation of Site-Specifically Spin-Labeled RNA by in Vitro Transcription Using an Expanded Genetic Alphabet" Methods Mol Biol.2022, 2439, 223-240.
H. Depmeier, E. Hoffmann, L. Bornewasser, S. Kath-Schorr* "Strategies for covalent labeling of long RNAs" ChemBioChem, 2021, 22, 2826-2847.
C. Domnick, F. Eggert, C. Wuebben, L. Bornewasser, G. Hagelueken, O. Schiemann*, S. Kath-Schorr* "EPR distance measurements on long non‐coding RNAs empowered by genetic alphabet expansion transcription" Angew. Chem. Int. Ed., 2020, 59, 7891-7896.
F. Eggert, S. Kath-Schorr* "A cyclopropene-modified nucleotide for site-specific RNA labeling using genetic alphabet expansion transcription" Chem. Commun., 2016, 52, 7284-7287.
C. Domnick, F. Eggert, S. Kath-Schorr* "Site-specific enzymatic introduction of a norbornene modified unnatural base into RNA and application in posttranscriptional labeling" Chem. Commun.2015, 51, 8253 - 8256.