Report Summary:For more than three decades, RNA has been known as an attractive macromolecule target for therapeutic purposes, But the identification of the drug optimization and target validation that have led to the approval of a few RNA-targeting therapeutics for clinical applications remain challenging. The key factors accounting for these successes will be addressed. The crucial aspects worth considering for further breakthroughs will be also discussed. Progress with therapeutic interventions aimed at targeting RNA has been slow, whether therapeutic agents are small or antisense oligonucleotides. The recent accomplishments in RNA targeting by small molecules can be traced back to structure-based drug design strategies against well-established targets. They were also made possible by phenotypic screening as it bypasses the false positives that typically arise when relying on binding assays only. In addition, such approaches owe their success to realistic expectations about what small molecules can reliably achieve upon binding RNA, such as interfering with a particular conformational changeover. Antibiotic resistance is, worldwide, a major health issue and the examples of antibiotic binding to the ribosomal RNA will be used to illustrate the key physico-chemical and structural parameters responsible for their efficacies. It is likely that future strategies of a similar nature will lead to the discovery of more drugs that regulate PNA-based functions.

Reported by:Prof. Eric Westhof is a member of the French Chinese Association for Advanced Talent Exchange, an internationally renowned molecular biologist, a member of the French Academy of Sciences, the German Academy of Sciences, and the European Academy of Sciences. He is also the Vice Chairman of the Alsace Regional Scientists Association. Dedicated to studying the correlation between RNA sequence structure and evolution for a long time, it enjoys a high national reputation in the field of RNA research. He conducted research on the kinetics and catalytic function of RNA through methods of crystallography and bioinformatics. He has extended the study of the physical and chemical characteristic structure and dynamics of RNA to its function and evolution, as well as predicting interactions with strong and specific molecules with therapeutic significance. Published 460 scientific papers in international authoritative academic journals such as Cell, Nature, Science, EMBOJ, PNAS, and served as an editor for Nuclear Acid Research, RNA, BBRC, and other journals, enjoying a high international reputation in the field of nucleic acid research.