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Prof. Dr. Thorsten Stafforst “Site-specific Manipulation of Nucleic Acids with (Bio)Chemical Tools”
October 9, 2017 @ 4:30 pm
Prof. Dr. Thorsten Stafforst
Interfaculty Institute of Biochemistry, Auf der Morgenstelle 15, 72076 Tübingen (Germany)
RNA modifications shape the expression of genetic information in many ways. Tools to manipulate single nucleobases at specific sites in selected transcripts in vivo are rare. We are engineering artifical RNA-guided proteins that allow to perform site-directed RNA editing in a highly rational and specific way (1-5). We will present new data that demonstrate highly specific and parallel editing of several endogenous transcripts, as well as data concercing the specificity, the potency and the duration of the effect. Furthermore we apply site-directed RNA editing for the switch of protein localization (5) and the ready implementation of photocaging (3, 5). Finally, we will present first data on the engineering of chemically stabilized antisense oligonucleotides that allow for the harnessing of endogenous ADARs to edit endogenous transcripts thereby avoiding the expression of an engineered protein. The latter was limiting in a recently published editing strategy (4). Furthermore, we have introduced psoralen as a photo-activatible crosslink for nucleic acids (6-7).
Keywords: Chemical Biology, Antisense Oligonucleotides, RNA Editing, Artificial Riboproteins, Photo Caging
Stafforst et al., Angew. Chem. Int. Ed. 2012, 51, 11166.
(2) Improving Directed RNA Editing In Vitro and in Cell Culture by Chemical Modification of the guideRNA
Vogel et al., Angew. Chem. Int. Ed. 2014, 53, 6267.
Hanswillemenke et al., J. Am. Chem. Soc. 2015, 137, 15 875-81.
Wettengel et al. Nucl. Acids Res. 2017, online
(5) Switching protein localization by site-directed RNA editing under control of light
Vogel et al., ACS Synth. Biol. 2017, online
Stafforst et al., Angew. Chem. Int. Ed. 2011, 50, 9483.
Stafforst et al., Angew. Chem. Int. Ed. 2013, 52, 12448.