We are developing novel chemical tools and are applying them to the study and control of RNA structure and function in living systems. We have designed and synthesized new cell-permeable reagents that react with RNA at accessible regions, enabling the mapping of RNA structure and interactions transcriptome-wide. We are also developing new caging technologies, called “RNA cloaking”. This work takes advantage of high-efficiency chemical reactions that we have developed with 2’-OH groups in RNA. We are also using this class of reactions to functionalize and label RNA, and to visualize and control RNA activity in cells and animals. Combined with next-gen sequencing and biophysical studies, we are using these methods to attain a better understanding of the complexities of RNA biology.