报告摘要：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.

报告人简介：Prof. Eric Westhof是法中高级人才交流协会会员，国际著名分子生物学家，法国科学院德国科学院、欧洲科学院三院院士，阿尔萨斯地区科学家联盟副主席。长期致力于研究RNA序列结构及进化的相关性，在RNA研究领域享有极高的国声誉。他通过结晶学和生物信息学的方法开展了关于RNA的动力学和催化功能的研究工作。他已经将RNA的物理化学特征结构和动力学研究扩展到其功能和进化方面，以及预测与具有治疗意义的强分子和特异性分子相互作用。在Cell, Nature, Science, EMBOJ, PNAS等国际权威学术期刊上发表科学论文460篇，担任Nucleic Acids Research, RNA, BBRC等期刊杂志编辑，在核酸研究领域享有极高的国际声誉。