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Design of metal-stabilized DNA and RNA nanoconstructs potentially applicable in medicine

Project description

Towards more stable DNA nanostructures for biomedical applications

DNA nanotechnology involves the design and construction of nanoscale structures and devices using DNA molecules as the building material. This field exploits the predictable self-assembly of DNA to create highly ordered and complex structures with precise control over their shape and function. Despite the potential of DNA nanomaterials, their instability under physiological conditions has limited their use in biomedical applications. Funded by the Marie Skłodowska-Curie Actions programme, the DNANOMETAL project aims to develop more stable DNA nanostructures by incorporating metal-mediated base pairing alongside classical base pairing. Researchers will design and analyse oligonucleotides that stabilise silver nanoclusters, creating stable nanoconstructs for use in vaccines and drug carriers

Objective

DNA nanotechnology can provide breakthroughs in various fields such as catalysis, nanofabrication, computation, bioimaging, drug delivery or cancer treatment. This approach is based on the idea that if single-stranded DNA sequences are not perfectly complementary, branched-stranded DNAs can be formed, from which complex 2D or 3D structures can be constructed with near-atomic precision by proper sequence design. Although DNA nanomaterials seem to be promising, the biomedical application is significantly challenged by the fact that current DNA - and especially RNA - nanostructures are unstable under physiological conditions, sensitive towards nucleases and oxidative damage as well. Therefore my main goal is to develop more stable DNA nanostructures that can later be used to stabilize vaccines or drug carriers. For this purpose I will use metal-mediated base pairing in addition to the classical Watson-Crick hydrogen base pairing. During the project I will design, purify and analyse oligonucleotides that stabilize silver nanoclusters (AgNCs) in the small size regime with mixed Ag0/AgI composition in order to achieve AgNC-oligonucleotide systems (nanoconstructs), that can remain stable even in the conditions of the human plasma, thus can be used later as vaccines or drug carriers. This approach is beyond state of the art since it was not even mentioned as a possible application of metal-incorporated DNA nanoconstructs in the most recent reviews of the field, although already existing data combined suggests, it could eliminate many of the issues of previous concepts. I will use modern separation, spectroscopy and structure quantification methods, as well as cellular studies, to design and characterise the system that best meets the criteria.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 214 934,40
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

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