Expanding the Biomaterials Space of DNA through Polymerization

dna是生命的基本组成部分，是一种天然的生物聚合物。然而，DNA研究和聚合物科学是独立的科学学科，交叉非常有限。这两个领域缺乏更深层次的整合，部分原因是DNA与合成聚合物的条件和试剂不相容。如果克服了这一障碍，DNA就可以自由地用来制造许多DNA-聚合物复合材料，这可能会带来比目前更好的疾病诊断、治疗和生物技术工具。在提议的项目中，PI的团队将开发一种与聚合物化学兼容的受保护DNA，一旦聚合物被制造出来，它就可以恢复到自然形态。利用受保护的DNA，将合成几种以前被认为是困难或不可能的基于DNA的聚合物来验证该方法。最后，一种DNA-肽共聚物将首次被保护的DNA激活，并将作为疫苗在人体细胞中进行制备和测试。这里开发的生物材料只是冰山一角；DNA和高分子科学的巨大知识基础的成功结合应该会产生无限的可能性。这些研究活动将与教育计划交织在一起，为研究生/本科生（包括来自缺乏研究能力的机构的本科生）提供多样化的实验室培训，并促进高中学生和STEM教师对科学相关职业的学习、意识和兴趣。基于dna的生物材料主要是通过固相反应或使用预先合成的寡核苷酸的水偶联来实现的。这两种方法对某些类型的结构都有限制，例如高度分支的结构和两亲结构。本提案的目标是通过消除核酸化学和聚合之间的障碍，极大地扩展使用寡核苷酸构建块可获得的生物材料的类型。为了实现这一目标，PI将设计化学掩盖的DNA结构，可以参与有机相的聚合反应（例如自由基，配位等）。被掩盖的DNA可以在聚合后的温和条件下恢复为天然磷酸二酯DNA。因此，通过这种方法，许多具有可控结构、组成、序列和端基功能的困难和/或前所未有的含dna聚合物成为可能。在准备的各种dna基材料中，肽- dna刷状共聚物将在生物学环境中作为自递送/佐剂肽疫苗进行研究。通过促进核酸与广泛的聚合反应的结合，具有技术上有用性质的新结构的多样性将成为可能。从教育的角度来看，这个项目的跨学科性质（设计、合成和材料/生物特性）是一个很好的教学工具，让所有层次的学生都参与到这个项目中来。PI将继续通过积极招聘、实习项目、课程开发和在线展示，为本科生和高中学生/教师创造研究机会。该奖项反映了美国国家科学基金会的法定使命，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。

NON-TECHNICAL SUMMARYDNA, a basic building block of life, is a form of natural biopolymer. Yet, DNA research and polymer science are separate scientific disciplines with very limited crossover. The lack of deeper integration of the two fields stems in part from the incompatibility of DNA with the conditions and reagents by which synthetic polymers are made. If this barrier is overcome, DNA can be freely used to craft many DNA-polymer composite materials, which can potentially lead to better disease diagnostics, therapeutics, and biotechnology tools than currently possible today. In the proposed project, the PI’s team will develop a form of protected DNA compatible with polymer chemistry, which can be restored to its natural form once the polymer has been made. Using the protected DNA, several DNA-based polymers previously deemed difficult or impossible will be synthesized to validate the methodology. Finally, a DNA-peptide copolymer, to be enabled by the protected DNA for the first time, will be prepared and tested as a vaccine in human cells. The biomaterials developed here represents only the tip of an iceberg; the successful marriage between DNA and the vast knowledge base of polymer science should result in limitless possibilities. These research activities will intertwine with educational programs to provide a diverse range of laboratory training to graduate/undergraduate students (including undergraduates from institutions lacking research capabilities) and to promote learning, awareness, and interest in science-related careers among high school students and STEM teachers.TECHNICAL SUMMARYDNA-based biomaterials are primarily achieved through solid-phase reactions or aqueous couplings using pre-synthesized oligonucleotides. Both methods pose limitations for certain types of constructs, such as highly branched architectures and amphiphilic structures. The goal of this proposal is to greatly expand the types of biomaterials accessible using oligonucleotide building blocks by removing the barriers between nucleic acid chemistry and polymerization. Towards this goal, the PI will design chemically masked DNA structures that can participate in polymerization reactions (e.g. free radical, coordination, etc) in the organic phase. The masked DNA can be restored to native phosphodiester DNA under mild conditions following polymerization. Thus, many difficult and/or unprecedented DNA-containing polymers with controlled architecture, composition, sequence, and end-group functionality are possible with this approach. Among the various DNA-based materials to be prepared, a peptide-DNA brush copolymer will be investigated in a biological setting as a self-delivering/adjuvanting peptide vaccine. By facilitating the marriage of nucleic acids with the vast range of polymerization reactions, a diversity of new structures with technologically useful properties will become possible. From the educational perspective, the cross-disciplinary nature of the project (design, synthesis, and materials/biological characterizations) is a great teaching tool for the students at all levels to be involved in the project. The PI will continue to create research opportunities for undergraduate students and high school students/teachers through active recruiting, internship programs, course development, and online presence.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.