LIN28 protein-RNA interaction as drug target

Small-molecule modulators of RNAs is a key activity of the group. With a multi-disciplinary team of collaborators, we are exploring the target potential of LIN28, an oncogenic RNA-binding protein (RBP) which controls biogenesis of let-7 miRNAs.

We began with characterization of the protein-RNA complex using NMR spectroscopy (external page Nat Struct Mol Biol 2012) and novel in vitro assays (external page Nucleic Acids Res 2013), as well as a miniaturized one for small-molecule screening.

One hit molecule (from 16'000 screened) was successfully validated in embryonic stem cells and cancer tumor spheres (external page ACS Chem Biol 2016).

Currently, we are investigating its use in two disease areas: prostate cancer (external page Cancer Res 2016) and myotonic dystrophies, in collaboration with clinical researchers at the Institute of Oncology Research, Bellinzona and the neurology dept. of LMU (DE), respectively.

Taken together, this project demonstrates a generic approach to assessing RBP-RNA interactions as drug targets for small molecule ligands. Specifically, it will allow us to determine whether the Lin28-RNA interaction is a valid drug target in any of several possible disease indications.