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Functional Materials Through Synthesis Informed Design

通过综合知情设计实现功能材料

基本信息

批准号：
1856414
负责人：
Paul Wender
金额：
$ 58.5万
依托单位：
Stanford University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1856414&HistoricalAwards=false
关键词：
Functional Materials Through Synthesis Informed

项目摘要

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Paul Wender of the Department of Chemistry at Stanford University. Professor Wender and his coworkers are investigating the design, synthesis, characterization, and evaluation of new materials that complex, protect, deliver, and release negatively-charged cargos such as RNA and DNA inside of living cells. These cargos are of unsurpassed importance in life science research, and these studies have potential utility in understanding cancer, protein therapy, allergy tolerization, neuroscience, universal flu vaccine development, disease detection and gene editing. These new materials are first-of-their-kind positively-charged carriers, designed to electrostatically grab on to the negatively-charged cargos. After cell entry, the positively-charged carriers change their physical properties, dynamically losing their positive charge and thereby releasing their negatively-charged cargo. The released RNA/DNA cargos contain a molecular message that is then translated by cellular machinery to produce proteins with research, diagnostic and other benefits. Coworkers trained in this program are becoming the next generation of scientific thought leaders and educators, joining over 300 former coworkers of Professor Wender who are now in leading positions in academia and the biotechnology industry. Many are also involved with science education at the college and high school levels. Professor Wender is also hosting visits from high school students, providing input on science projects, and lecturing at several science-for-non-scientist events. He has pioneered a new undergraduate course on scientific communication and innovation (SCI) (https://news.stanford.edu/2017/11/30/undergraduates-start-popular-science-publication/), engaging undergraduates in teaching high school and college students about science. This has led to a new undergraduate organization that is sharing and celebrating the fun, excitement and value of science through their web site and other media (https://fascinatepublication.org). In this project, Professor Wender is studying the design, synthesis, and evaluation of new dynamic functional materials for the delivery of probes, imaging agents, catalysts, and other cargo across biological barriers. To accomplish this, he is developing new reactions, reagents, and catalysts for synthesis, and developing machine learning for retrosynthetic analysis and material design. The intellectual foundation of these studies is intrinsically chemical - synthesis, computer learning, and materials science, with potentially profound consequences in life science research. Increasingly in chemistry and in Professor Wender's research, mechanistic and synthetic chemistry have been integrated into studies directed at the design, synthesis and evaluation of functional materials of scientific and societal value (e.g. catalysts, imaging agents, sensors, molecular machines, diagnostics, drug delivery systems). The proposed research is primarily directed at the design, synthesis and evaluation of dynamic materials that complex, protect, deliver and release in cells polyanions such as RNA and DNA, representing the single most significant bottleneck to the advancement of many new RNA/DNA technologies. In this program, new classes of materials are being studied which serve initially as cations that electrostatically complex polyanions and subsequently change their physical properties, through an O-to-N acyl shift mechanism, thereby converting to neutral byproducts and releasing their polyanionic RNA/DNA cargo. The delivery vehicles, referred to as charge-altering releasable transporters (CARTs), represent a novel challenge in synthesis as unlike most synthetic targets which are selected for their stability, CARTs are designed to degrade. This project is synthesizing unprecedented monomeric, dimeric and dendrimeric CARTs (non-oligomeric CARTs), exploring the factors that influence their performance and the rules for their use in delivering cargos into living cells. These intrinsically chemical and synthetic studies are directed at goals that enable new opportunities in biology, imaging, materials science, and medicine.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，NSF化学部的化学合成计划正在支持斯坦福大学化学系的Paul Wender教授的研究。Wender教授和他的同事正在研究新材料的设计，合成，表征和评估，这些新材料可以复合，保护，递送和释放带负电荷的货物，如活细胞内的RNA和DNA。这些货物在生命科学研究中具有无与伦比的重要性，这些研究在理解癌症、蛋白质治疗、过敏耐受、神经科学、通用流感疫苗开发、疾病检测和基因编辑方面具有潜在的实用性。这些新材料是第一种带正电荷的载体，旨在静电地抓住带负电荷的货物。在进入细胞后，带正电荷的载体改变其物理性质，动态地失去其正电荷，从而释放其带负电荷的货物。释放的RNA/DNA货物包含分子信息，然后由细胞机器翻译以产生具有研究，诊断和其他益处的蛋白质。在这个程序中培训的同事正在成为下一代的科学思想领袖和教育工作者，加入温德教授的300多名前同事谁是现在在学术界和生物技术行业的领先地位。许多人还参与了大学和高中的科学教育。温德教授还接待了高中学生的访问，提供科学项目的投入，并在几个科学非科学家活动中讲课。他开创了一门关于科学传播与创新（SCI）的新本科课程（https：//news.stanford.edu/2017/11/30/undergraduates-start-popular-science-publication/），让本科生参与教授高中和大学生科学知识。这导致了一个新的本科生组织，通过他们的网站和其他媒体（https：//www.example.com）分享和庆祝科学的乐趣，兴奋和价值。fascinatepublication.org在这个项目中，温德教授正在研究新的动态功能材料的设计，合成和评估，用于传递探针，成像剂，催化剂和其他货物跨越生物屏障。为了实现这一目标，他正在开发用于合成的新反应、试剂和催化剂，并开发用于逆合成分析和材料设计的机器学习。这些研究的知识基础本质上是化学合成，计算机学习和材料科学，在生命科学研究中具有潜在的深远影响。在化学和Wender教授的研究中，机械和合成化学越来越多地被整合到针对具有科学和社会价值的功能材料（例如催化剂，成像剂，传感器，分子机器，诊断，药物输送系统）的设计，合成和评估的研究中。拟议的研究主要针对动态材料的设计，合成和评估，这些材料在细胞中复合，保护，递送和释放聚阴离子，如RNA和DNA，这是许多新RNA/DNA技术进步的最重要瓶颈。在该计划中，正在研究新的材料类别，这些材料最初作为阳离子，静电络合聚阴离子，随后通过O-至-N酰基转移机制改变其物理性质，从而转化为中性副产物并释放其聚阴离子RNA/DNA货物。被称为电荷改变可释放转运蛋白（CART）的递送载体代表了合成中的新挑战，因为与大多数因其稳定性而选择的合成靶标不同，CART被设计为降解。该项目正在合成前所未有的单体，二聚体和树枝状CART（非寡聚CART），探索影响其性能的因素以及将货物运送到活细胞中的规则。这些本质上的化学和合成研究旨在实现生物学、成像、材料科学和医学领域的新机遇。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。