DNA, 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.
DNA-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.
