Final Report Summary - ESCODNA (European School of DNA Nanotechnology)
DNA Nanotechnology is an emerging interdisciplinary area with the potential to become a leading technological foundation for the development of future medicines, diagnostic tools, materials, optics and electronics. The field has evolved primarily in the USA. However, in recent years a number of European research groups, which are part of the European School of DNA Nanotechnology (EScoDNA) ITN network, have contributed significantly to this new research field.
EScoDNA was thus established with the overall purpose of strengthening research in DNA Nanotechnology in Europe by training young researchers to become future leaders in this strategic interdisciplinary research area. In addition the purpose was to establish closer connections between the leading research groups and the few companies in this area through collaboration, joint meetings and student exchanges.
DNA nanotechnology is based on the unique self-assembly properties of DNA and other nucleotide derivatives which allow the rational design and formation of nanoscale structures with predictable geometry and function. It includes studies of the basic self-assembly properties of nucleobases and the cooperative assembly of large assemblies of hundreds of DNA strands.
In the outline of the research projects the main objectives to study, were the design of functional DNA nanostructures, to integrate other materials than DNA in DNA nanostructures and to apply the hybrid structures to life science and medicine.
One of the key results of EScoDNA has been the construction of a DNA origami-based force sensors where single-stranded DNA acts as entropic spring. These force sensors serve as a new tool to study the activity of DNA-interacting. The results were published in Science in 2016 by the partner and ESR at LMU. Another advanced functional DNA structure, a DNA vault that can contain proteins and control their function was developed by one of the Aarhus University ESRs and the resulting manuscript is submitted to a high impact journal. At the company baseclick a new so-called DNA chain-armor structure was designed, which provided much higher stability, since the DNA strands are cyclized and this work was published in Angewandte Chemie. A related study where disulfides were used to cyclize the DNA strands was developed by one of the ESRs at Aarhus University and published in ChemBioChem. For the understanding of dynamic DNA structures called DNA walkers one of the ESRs at University of Oxford developed a formal language and design principles of autonomous DNA walker circuits which was published in ACS Synth. Biol. in 2016.
For the integration of DNA nanostructures with other materials several groups have produced DNA or RNA conjugates of proteins. The interaction of DNA origami structures with various surfaces was also studied by ESRs at TUM and Aarhus University resulting in papers in Angewandte Chemie and in Small. Another important aspect has been the interaction with and integration of structures in phospholipid membranes. The ESRs a LMU and TUM contributed with papers in ACS Nano and Nanoletters on among other things membrane-assisted growth of DNA origami nanostructure arrays.
An important aspect of the application of DNA nanostructures to life science and medicine is the delivery of the structures to cells. ESRs at TUM and LMU have investigated uptake of DNA nanostructures in cells by various mechanisms and this has resulted in publications in Nano Letters, Biomaterials and Nanomaterials. In another spectacular result one of the ESRs at Karolinska Institutet designed a DNA nanostructure with two ligands separated at different distances and studied the spatial control of membrane receptor function. This work was published in Nature Materials.
In addition to the results mentioned above a number of manuscripts resulting from EScoDNA research are currently in preparation.
The results generated by the research conducted by the ESRs and ERs of EScoDNA will have impact on both academia and industry. New enabling technologies have been delivered, which will be essential to the development of the field and for realisation of both fundamental scientific goals and industrial goals in the area of design of functional and dynamic DNA nanostructures, and integrating other materials in DNA nanostructures.
The research at EScoDNA has also led to potential real life application. In one example the research at baseclick GmbH has indirectly lead to the patenting of a method and establishment of a spin-off company by the supervisor at baseclick. Furthermore, the technologies developed by the ESR at Vipergen have been integrated in Vipergen’s Yoctoreactor technology, which will be used to develop new drug leads. Development of new selection processes for small molecule binders to modified four way junctions at AU may lead to better small molecule sensors for diagnostics.
In EScoDNA we have in addition to producing several high impact results, trained a generation of 14 ESRs and 2 ERs in the highly interdisciplinary field of DNA Nanotechnology. Besides the training, then the collaboration between the partners on this project has undoubtedly strengthened the competitiveness of the European Union in this important field of disruptive research. DNA nanotechnology holds the key to future advanced research since it provides unmatched degree of control of structure and function at the nanoscale. Therefore there is a high plausibility that DNA nanotechnology will become a future key technology of this century with enormous economic impact. Hence, the EScoDNA Initial Training Network has been of great benefit to the future career of the young researchers. This network enhanced their skills and knowledge in this fascinating field of research.
Website: https://escodna.eu/
EScoDNA was thus established with the overall purpose of strengthening research in DNA Nanotechnology in Europe by training young researchers to become future leaders in this strategic interdisciplinary research area. In addition the purpose was to establish closer connections between the leading research groups and the few companies in this area through collaboration, joint meetings and student exchanges.
DNA nanotechnology is based on the unique self-assembly properties of DNA and other nucleotide derivatives which allow the rational design and formation of nanoscale structures with predictable geometry and function. It includes studies of the basic self-assembly properties of nucleobases and the cooperative assembly of large assemblies of hundreds of DNA strands.
In the outline of the research projects the main objectives to study, were the design of functional DNA nanostructures, to integrate other materials than DNA in DNA nanostructures and to apply the hybrid structures to life science and medicine.
One of the key results of EScoDNA has been the construction of a DNA origami-based force sensors where single-stranded DNA acts as entropic spring. These force sensors serve as a new tool to study the activity of DNA-interacting. The results were published in Science in 2016 by the partner and ESR at LMU. Another advanced functional DNA structure, a DNA vault that can contain proteins and control their function was developed by one of the Aarhus University ESRs and the resulting manuscript is submitted to a high impact journal. At the company baseclick a new so-called DNA chain-armor structure was designed, which provided much higher stability, since the DNA strands are cyclized and this work was published in Angewandte Chemie. A related study where disulfides were used to cyclize the DNA strands was developed by one of the ESRs at Aarhus University and published in ChemBioChem. For the understanding of dynamic DNA structures called DNA walkers one of the ESRs at University of Oxford developed a formal language and design principles of autonomous DNA walker circuits which was published in ACS Synth. Biol. in 2016.
For the integration of DNA nanostructures with other materials several groups have produced DNA or RNA conjugates of proteins. The interaction of DNA origami structures with various surfaces was also studied by ESRs at TUM and Aarhus University resulting in papers in Angewandte Chemie and in Small. Another important aspect has been the interaction with and integration of structures in phospholipid membranes. The ESRs a LMU and TUM contributed with papers in ACS Nano and Nanoletters on among other things membrane-assisted growth of DNA origami nanostructure arrays.
An important aspect of the application of DNA nanostructures to life science and medicine is the delivery of the structures to cells. ESRs at TUM and LMU have investigated uptake of DNA nanostructures in cells by various mechanisms and this has resulted in publications in Nano Letters, Biomaterials and Nanomaterials. In another spectacular result one of the ESRs at Karolinska Institutet designed a DNA nanostructure with two ligands separated at different distances and studied the spatial control of membrane receptor function. This work was published in Nature Materials.
In addition to the results mentioned above a number of manuscripts resulting from EScoDNA research are currently in preparation.
The results generated by the research conducted by the ESRs and ERs of EScoDNA will have impact on both academia and industry. New enabling technologies have been delivered, which will be essential to the development of the field and for realisation of both fundamental scientific goals and industrial goals in the area of design of functional and dynamic DNA nanostructures, and integrating other materials in DNA nanostructures.
The research at EScoDNA has also led to potential real life application. In one example the research at baseclick GmbH has indirectly lead to the patenting of a method and establishment of a spin-off company by the supervisor at baseclick. Furthermore, the technologies developed by the ESR at Vipergen have been integrated in Vipergen’s Yoctoreactor technology, which will be used to develop new drug leads. Development of new selection processes for small molecule binders to modified four way junctions at AU may lead to better small molecule sensors for diagnostics.
In EScoDNA we have in addition to producing several high impact results, trained a generation of 14 ESRs and 2 ERs in the highly interdisciplinary field of DNA Nanotechnology. Besides the training, then the collaboration between the partners on this project has undoubtedly strengthened the competitiveness of the European Union in this important field of disruptive research. DNA nanotechnology holds the key to future advanced research since it provides unmatched degree of control of structure and function at the nanoscale. Therefore there is a high plausibility that DNA nanotechnology will become a future key technology of this century with enormous economic impact. Hence, the EScoDNA Initial Training Network has been of great benefit to the future career of the young researchers. This network enhanced their skills and knowledge in this fascinating field of research.
Website: https://escodna.eu/