Objective
As a Maria Skłodowska-Curie Fellow, I aim to develop formulated next-generation RNA replicons that are designed to overcome the limiting initial type I interferon response that inhibits amplification and protein expression. RNA replicons are currently a cutting edge nucleic acid platform for delivery of vaccines and therapeutics, as they do not require penetration into the nucleus like plasmid DNA, but possess self-amplification properties that results in more efficient protein expression than messenger RNA. While pDNA and mRNA have have demonstrated excellent results with low doses when tested in mice doses must be scaled up by two orders of magnitude to mirror these effects in nonhuman primates. This disparity reflects a non-linear dose-response relationship, where increased doses are associated with triggering of an interferon cascade which restricts protein expression. Under the supervision of Prof. Robin Shattock, a world leader in translational vaccines and clinical trials at Imperial College London, I aim to overcome this translational barrier for RNA replicons by focusing on maximizing protein expression. I intend to engineer synergistic increases in the amplification of RNA replicons through a combination of molecular modifications designed to minimize interferon response and co-delivery with synthetic single-strand oligonucleotides known to inhibit the interferon pathway. These molecular adaptions will be paired with a novel delivery polymer that directly incorporates oligonucleotides into the RNA polyplex, thus ensuring co-localization: to be synthesized in collaboration with Prof. Molly Stevens, a world leader in polymeric biomaterials, during a secondment at the Karolinska Institutet. This project is the first demonstration of synergistic molecular and formulation design to address the non-linear dose-response relationship, and could impact scalability of RNA vaccines and therapeutics making them more affordable and available in Europe and worldwide.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences zoology mammalogy primatology
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences genetics RNA
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2017
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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.
SW7 2AZ London
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.