| With our contributions to DNA block copolymers (DBCs), we have opened a new field of interdisciplinary research at the intersection of polymer chemistry, biology and nanoscience. Within this proposal, we intend to apply our expertise with linear DNA block copolymers to a new nucleocopolymer architecture, DNA networks. This will again entail a synergy of synthetic methods from organic and polymer chemistry with enzymatic methods and techniques from molecular biology. Our efforts will not only explore new covalently-bonded polymer topologies but also extend the range of self-assembled supramolecular structures accessible with DBCs. Current progress in this direction has yielded spherical and rod-like DBC micelles. In this proposal we further envisage membranes and vesicles generated by macromolecular DNA amphiphiles. A special focus will be the manipulation of vesicle structures by hybridization, which leads to aggregation, division and fusion, the latter resulting in multistep chemical reactions induced by content mixing of the compartments. A major part of the proposal addresses potential applications of DBC architectures in the fields of nucleic acid and biomolecule detection as well as drug delivery. We will produce selective and sensitive nucleic acid probes employing DBCs with highly emissive conjugated polymer segments or based on novel fluorogenic DNA-templated reactions or transcription factors. Plans for potential delivery systems include virus capsids encapsulating DBC micelles. This represents a significant improvement over our current DBC drug delivery platform with regard to stability and targeting. This system simultaneously solves a pressing problem in virus-based delivery, namely a universal and efficient strategy for loading these potent nanocontainers with small molecular weight drugs and pharmaceutically active biologicals covering a broad range of physicochemical parameters. |
