[4-19]What can Chemistry do in Translational Medicine?
时间：2013-04-18来源：苏州大学药学院本科教学网点击：0
报告题目：What can Chemistry do in Translational Medicine?
Designing Advanced Materials for Systemic Delivery of RNAi Therapeutics
报告人：Dr. Yunlong Zhang（Koch Institute for Cancer Research /Massachusetts Institute of Technology Children’s Hospital Boston / Harvard Medical School）
报告时间：2013年4月19日（星期五）下午2:30
报告地点：独墅湖校区二期云轩楼2301室
报告摘要：
With a growing understanding of the biological mechanism of disease, many genes and proteins have been found to play significant roles. Thus direct application of genes and proteins as therapeutical agents in clinic holds great potential for translational medicine. However, the major challenges are the poor pharmacokinetics of these biologic molecules and their lack of abilities to efficiently across the cell membrane. In order to facilitate the transportation problems, design and synthesis of biomaterials are crucial for drug delivery systems (DDS).
Materials functions are often achieved through their structural or chemical changes at the molecular level. Therefore an understanding of chemical mechanism is often necessary for materials design. In the first part, I will discuss how a reaction mechanism is studied by research on various reactive intermediates. A detailed understanding of several reaction mechanisms has been obtained using advanced experimental and computational tools. In the second part, I will talk about how structural and mechanistic insights are used in developing biomaterials for systemic delivery of small interfering RNAs (siRNAs). A library of materials based on modified amino acids was synthesized and evaluated for siRNA delivery, and this study led to the discovery of a novel structural scaffold which was characterized with advanced NMR techniques. In order to overcome the limitation of toxicity, lipid-modified amino sugars were designed and the formulated nanoparticles were found to induce near-complete gene silencing at low siRNA doses both in vitro and in vivo. Further studies indicated that materials have low toxicities after systemic administration. Together, these studies provided materials with unprecedented therapeutical index and have the potential to accelerate translating RNAi therapeutics into clinic.
