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
Key words
RIBOTAC - targeted degradation - RNase - miR-21
Significance
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.
Comment
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.
