Unveiling the druggable RNA targets and small molecule therapeutics |
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Authors: | Joanna Sztuba-Solinska Gabriela Chavez-Calvillo Sabrina Elizabeth Cline |
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Institution: | Department of Biological Sciences, Auburn University, 120 W. Samford Ave, Rouse Life Sciences Building, Auburn, AL 36849, USA |
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Abstract: | The increasing appreciation for the crucial roles of RNAs in infectious and non-infectious human diseases makes them attractive therapeutic targets. Coding and non-coding RNAs frequently fold into complex conformations which, if effectively targeted, offer opportunities to therapeutically modulate numerous cellular processes, including those linked to undruggable protein targets. Despite the considerable skepticism as to whether RNAs can be targeted with small molecule therapeutics, overwhelming evidence suggests the challenges we are currently facing are not outside the realm of possibility. In this review, we highlight the most recent advances in molecular techniques that have sparked a revolution in understanding the RNA structure-to-function relationship. We bring attention to the application of these modern techniques to identify druggable RNA targets and to assess small molecule binding specificity. Finally, we discuss novel screening methodologies that support RNA drug discovery and present examples of therapeutically valuable RNA targets. |
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