Magnetically-Activated Nucleic Acids

Lead Research Organisation: University of Oxford


Nucleic acids carry genetic information and serve as the fundamental building blocks for life. They also form the basis of many therapeutic technologies as the active pharmaceutical ingredient, including the vaccinations for SARS-CoV-2.

There are two major challenges in the application of nucleic acids: delivering the negatively charged molecules into living cells and ensuring they target specific areas of the body. The latter can be achieved by either targeted delivery or targeted activation. In particular targeted activation is desirable to inhibit the function of nucleic acids until they are remotely activated at the target site and prevent off-target effects and damage to the healthy cells. Remote stimuli such as light, temperature and magnetism allow for the precise, spatial and temporal control of nucleic acids without the need for invasive surgery. The most prevalent remote stimulus is light and relies on light sensitive molecules called photocages to block nucleic acid function.

Magnetism offers improved tissue penetration depth over light, having minimal interaction with the surrounding water molecules. Subjecting magnetic nanoparticles to an alternating magnetic field causes localised heating at the surface of the nanoparticle whilst the temperature of the bulk environment remains constant. This localised heating termed hyperthermia is currently used to treat tumours. This hyperthermia can also be used to release therapeutic molecules attached to the surface of the magnetic nanoparticle, via a thermally sensitive linker. The simultaneous diagnosis by magnetic resonance imaging (MRI) and the delivery of therapeutic nucleic acids could be achieved by combining magnetic nanoparticles with multiple nucleic acid technologies.

This project aims to design and synthesise magnetically-activated nucleic acids. The target nucleic acid will be attached to the surface of magnetic nanoparticles via a heat labile linker, rending it inaccessible for downstream applications. Exposure to an alternating magnetic field will cause localised heating at the surface of the magnetic nanoparticle and release of the nucleic acid. The activated nucleic acid will then be accessible for downstream biological processes. The system will be initially tested in cell-free systems before further application in synthetic and living cells.

This project falls within the EPSRC 'physical sciences' research theme.

Planned Impact

The primary impact of the OxICFM CDT will be the highly-trained world-class scientists that it delivers. This impact will encompass both the short term (during their doctoral studies), the medium term (subsequent employment) and ultimately the longer timescale defined by their future careers and consequent impact on science, engineering and policy in the UK.

The impact of OxICFM students during their doctoral studies will be measured by the culture change in graduate training that the Centre brings about - in working at the interface between inorganic synthesis and manufacturing, and fostering cross-sector industry/academia working practices. By embedding not only from larger companies, but also SMEs, we have developed a training regime that has broader relevance across the sector, and the potential for building bridges by fostering new collaborations spanning enormous diversity in scientific focus and scale. Moreover, at a broader level, OxICFM offers to play a unique role as a major focus (and advocate) for manufacturing engagement with academic inorganic synthetic science in the UK.

From a scientific perspective, OxICFM will be uniquely able to offer a broad training programme incorporating innovative and challenging collaborative projects spanning all aspects of fundamental and applied inorganic synthesis, both molecular and materials based (40+ faculty). These will address key challenges in areas such as energy provision/storage, catalysis, and resource provision/renewal necessary to enhance the capability and durability of UK plc in the medium term. To give some idea of perspective, the output from previous CDTs in Oxford's MPLS Division include two start-up companies and in excess of 30 patents.

It is not only in the industrial and scientific realms that students will have impact during their timeframe of their doctorate. Part of the training programme will be in public engagement: team-based challenges in resource development/training and outreach exercises/implementation will form part of the annual summer school. These in turn will constitute a key part of the impact derived from the CDT by its engagement with the public - both face-to-face and through electronic/web-based media. As the centre matures, our aspiration is that our students - from diverse backgrounds - will act as ambassadors for the programme and promote even higher levels of inclusion from all parts of society.

For our partners, and businesses both large and small in the manufacturing sector, it will be our students who are considered the ultimate output of the OxICFM CDT. Our programme has been shaped by the need of such companies (frequently expressed in preliminary discussions) to recruit doctoral graduates who can apply themselves to a broad spectrum of multi-disciplinary challenges in manufacturing-related synthesis. OxICFM's cohort-based training programme integrates significant industry-led training components and has been designed to deliver a much broader skill set than standard PhD schemes. The current lack of CDT training at the interface of inorganic chemistry and manufacturing (and the relevance of inorganic molecules/materials to numerous industrial sectors) heightens the need for - and the potential impact of - the OxICFM CDT. Our students will represent a tangible and valuable asset to meet the long-term skills demand for scientists to develop new materials and nanotechnology identified in the UK Government's 2013 Foresight report.

In the longer term, the broad and relevant training delivered by OxICFM, and the uniquely wide perspective of the manufacturing sector it will deliver, will allow our graduates to obtain (and thrive in) positions of significant responsibility in industry and in research facilities/institutes. Ultimately we believe that many will go on to be future research leaders, driving innovation and changing research culture, and thereby making a lasting contribution to the UK economy.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023828/1 31/03/2019 29/09/2027
2580992 Studentship EP/S023828/1 30/09/2021 29/09/2025 Ellen Parkes