Long and short non-coding RNAs regulate gene expression in healthy and diseased cellular states. Their mutation or abnormal expression is often observed in chronic diseases ranging from cancer to neurodegeneration. We have shown that a single nucleotide polymorphism within the promoter-associated transcript regulates expression of the tumor suppressor E-cadherin by causing an RNA structural switch which affects differential recruitment of epigenetic enzymes and results in differential prostate cancer progression. Metastable, switchable RNA structures within non coding RNAs provide attractive but unexploited targets for pharmaceutical intervention. We target non coding RNAs by using cyclic peptides and engineered proteins to inhibit expression of the oncogenic microRNA miR-21. This chemistry provides unprecedented affinity and specificity for stem-loop structures that constitute the dominant structural element within non-coding RNAs, penetrate cells readily and allow demonstration of cellular activity through RNA target engagement.<br/>

Structural plasticity in disease and pharmaceutical targeting of non-coding RNAs

255th National Meeting (2018)

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