Synfacts 2020; 16(04): 0463
DOI: 10.1055/s-0040-1707575
Chemistry in Medicine and Biology
© Georg Thieme Verlag Stuttgart · New York

RIBOTACs – Targeted Degradation of RNA

Dirk Trauner
Klaus-Peter Ruehmann
Costales MG, Aikawa H, Li Y, Childs-Disney JL, Abegg D, Hoch DG, Velagapudi SP, Nakai Y, Khan T, Wang KW, Yildirim I, Adibekian A, Wang ET, Disney MD. * The Scripps Research Institute, Jupiter, USA
Small-Molecule Targeted Recruitment of a Nuclease to Cleave an Oncogenic RNA in a Mouse Model of Metastatic Cancer.

Proc. Natl. Acad. Sci. U.S.A. 2020;
117: 2406-2411
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Publication History

Publication Date:
18 March 2020 (online)



Oncogenic micro RNAs are important components of cancer cells since they heavily regulate the expression levels of various proteins. Selective degradation of these miRNAs could be of great potential for cancer therapies. Here, the authors expanded the concept of RIBOTACs, which enables the selective small-molecule targeted degradation of RNA. Mouse models showed inhibition of metastasis progression following administration of miR-21 RIBOTAC.



The RNA-binding domains and the RNase recruiting fragment were linked to the backbone via copper-catalyzed ‘click’ reactions and a peptide coupling, respectively. The final RIBOTAC was demonstrated to bind the cancer-causing pre-miR-21 with great selectivity over other RNA transcripts and was effective in RNase recruitment and target degradation.