Download or read book Strategies to Optimize the Selectivity of Small Molecules Targeting RNA written by Matthew G. Costales and published by . This book was released on 2019 with total page 543 pages. Available in PDF, EPUB and Kindle. Book excerpt: Potential RNA targets in the transcriptome are numerous but there are limited examples of small molecules that target RNA and affect its function. Sequencing studies have shown that 80% of our genome is transcribed but only 1-2% directly encodes protein. These and other studies show that non-coding RNAs play myriad roles in biological processes. One example is microRNAs (miRNAs), which are small, non-coding RNAs that regulate gene expression by targeting mRNAs for degradation or translational repression. Not surprisingly, dysregulation of RNAs, including miRNAs, can cause disease. The current strategy to target RNAs is through complementary base pairing with antisense oligonucleotides. Oligonucleotides are hampered, however, by their poor permeability and lack of effective delivery systems, elicitation of an immune response and other off-target effects, and difficulty producing large amounts, reducing their therapeutic potential. An alternative approach is to target structural elements of RNA with small molecules. Designing small molecules, however, is much more difficult than the simple base pairing rules used to design oligonucleotides, thus limiting their use in chemical biology and medicinal fields. Herein, I describe strategies to use sequence-based rational design to develop small molecules that selectively target RNA. As small molecule modulators of RNA are highly desirable, I also describe the development of approaches to probe their target engagement and selectivity. Additionally, I detail an emerging targeted degradation strategy to recruit endogenous ribonucleases to cleave specific transcripts.