Final Report Summary - NANO-DNA (Functional DNA nanomaterials)
Solid phase DNA synthesis is certainly one of the most influential developments of the last century. Together with the understanding of DNA structure and function, not only biology and molecular genetics have advanced significantly, but also new emerging fields such as bio-nanotechnology would not have evolved. The detailed understanding of the structure of DNA makes it possible to design DNA sequences which spontaneously form objects through complementary nucleobase recognition. Taking DNA out of its biological environment and using it as a most versatile construction material for nano-architectures gives this bio-molecule an entirely new perspective.
The use of modified nucleosides in DNA nanotechnology is still in its infancy. Several successful implementations have been demonstrated recently, and integrated function becomes more and more accessible. However, the major step from “simple” dsDNA with incorporated modifications to functional DNA nanostructures including these functionalities has yet to be achieved. Only very few examples to demonstrate the feasibility of this approach exist. Our project will significantly advance the field by combining DNA nano-technology with chemically modified nucleosides, incorporating designer molecules to add specific programmed function, and apply these systems to make ground breaking advances in electronics, photovoltaics and medicine. In this respect, every single achievement in the research tasks is a major advancement in the related fields.
The first task was the most important in developing the techniques for creating molecular wires along precisely laid-out tracks and will be the first of its kind. We designed and synthesised this porphyrin DNA wires successfully. If the next step of study confirmes the unique properties of the system, it will be mined that our scaffold is an excellent starting material for nanoscale breadboards for molecular electronic or plasmonic circuits.
The second research task was the use of DNA to form chiral chromophore arrays based on our porphyrin building block system that can be used as a part of energetic cascades. We synthesised several similar systems with different number of porphyrin units. One of them was applied as a mediator in energy transfer between electronically active components in self-assembled light tubes using bio-templating, and the second was used as a wire for cross-membrane electron transport (see Figure 1 and 2). These results confirmed that porphyrin DNA is useful in the formation of an efficient antenna system, which is complementary to existing dendrimer-based porphyrin antennae but has a more modular component to achieve better optical spectrum coverage. These studies lay the foundation for an entirely novel approach in dye sensitisation of solar cells and in the future creation of novel, DNA based electronic devices.
In the last part of project (RT3) we demonstrate that porphyrins can be used in cancer treatment. Previous studies showed that these units can be used in photodynamic therapy, so we wanted to develop this approach with additionally increasing their selectivity. The best way for the realization of this plan was to introduce porphyrins by a process that is specific to cancer cells, i.e. elongation of DNA chains by telomerase that causes immortality of cancer cells. We designed and obtained the modified porphyrin monomer which is introduced in DNA by enzymes the same way as natural nucleosides do (see Figure 3). These results are promising in obtaining a highly efficient skin cancer therapy, combining telomerase inhibition with photodynamic therapy, which may also be applicable to other types of cancer.
The use of modified nucleosides in DNA nanotechnology is still in its infancy. Several successful implementations have been demonstrated recently, and integrated function becomes more and more accessible. However, the major step from “simple” dsDNA with incorporated modifications to functional DNA nanostructures including these functionalities has yet to be achieved. Only very few examples to demonstrate the feasibility of this approach exist. Our project will significantly advance the field by combining DNA nano-technology with chemically modified nucleosides, incorporating designer molecules to add specific programmed function, and apply these systems to make ground breaking advances in electronics, photovoltaics and medicine. In this respect, every single achievement in the research tasks is a major advancement in the related fields.
The first task was the most important in developing the techniques for creating molecular wires along precisely laid-out tracks and will be the first of its kind. We designed and synthesised this porphyrin DNA wires successfully. If the next step of study confirmes the unique properties of the system, it will be mined that our scaffold is an excellent starting material for nanoscale breadboards for molecular electronic or plasmonic circuits.
The second research task was the use of DNA to form chiral chromophore arrays based on our porphyrin building block system that can be used as a part of energetic cascades. We synthesised several similar systems with different number of porphyrin units. One of them was applied as a mediator in energy transfer between electronically active components in self-assembled light tubes using bio-templating, and the second was used as a wire for cross-membrane electron transport (see Figure 1 and 2). These results confirmed that porphyrin DNA is useful in the formation of an efficient antenna system, which is complementary to existing dendrimer-based porphyrin antennae but has a more modular component to achieve better optical spectrum coverage. These studies lay the foundation for an entirely novel approach in dye sensitisation of solar cells and in the future creation of novel, DNA based electronic devices.
In the last part of project (RT3) we demonstrate that porphyrins can be used in cancer treatment. Previous studies showed that these units can be used in photodynamic therapy, so we wanted to develop this approach with additionally increasing their selectivity. The best way for the realization of this plan was to introduce porphyrins by a process that is specific to cancer cells, i.e. elongation of DNA chains by telomerase that causes immortality of cancer cells. We designed and obtained the modified porphyrin monomer which is introduced in DNA by enzymes the same way as natural nucleosides do (see Figure 3). These results are promising in obtaining a highly efficient skin cancer therapy, combining telomerase inhibition with photodynamic therapy, which may also be applicable to other types of cancer.