Expanding the Biomaterials Space of DNA through Polymerization

非技术的SUMMARYDNA是生命的基本组成部分，是一种天然生物聚合物。然而，DNA研究和聚合物科学是两个独立的科学学科，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与制造合成聚合物的条件和试剂不兼容。如果这一障碍被克服，DNA可以自由地用于制作许多DNA聚合物复合材料，这可能导致比目前可能的更好的疾病诊断、治疗和生物技术工具。在拟议的项目中，PI的团队将开发一种与聚合物化学兼容的受保护DNA形式，一旦聚合物制造完成，这种DNA就可以恢复到其自然形式。利用受保护的DNA，将合成几种以前被认为困难或不可能的DNA聚合物，以验证该方法。最后，将首次利用受保护的DNA制备DNA-多肽共聚物，并将其作为疫苗在人类细胞中进行测试。这里开发的生物材料只是冰山一角；DNA与聚合物科学的巨大知识基础之间的成功结合应该会带来无限的可能性。这些研究活动将与教育项目交织在一起，为研究生/本科生(包括缺乏研究能力的机构的本科生)提供各种实验室培训，并促进高中生和STEM教师对与科学相关的职业的学习、意识和兴趣。TECHNICAL SUMMARYDNA生物材料主要通过使用预合成的寡核苷酸进行固相反应或水相偶联来实现。这两种方法都对某些类型的结构提出了限制，例如高度分支的结构和两亲性结构。这项提议的目标是通过消除核酸化学和聚合之间的障碍，极大地扩大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将设计能够参与有机相聚合反应(如自由基、配位等)的化学掩蔽DNA结构。掩蔽后的DNA可以在温和的条件下聚合后恢复为天然的磷酸二酯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/或史无前例的含DNA聚合物成为可能。在将要制备的各种基于DNA的材料中，将在生物环境中研究一种多肽-DNA刷状共聚物作为自递送/佐剂多肽疫苗。通过促进核酸与广泛的聚合反应的结合，具有技术上有用特性的各种新结构将成为可能。从教育的角度来看，该项目的跨学科性质(设计、合成和材料/生物学特性)是各级学生参与该项目的一个很好的教学工具。PI将继续通过积极的招聘、实习计划、课程开发和在线展示为本科生和高中生/教师创造研究机会。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.