Project description
Bacterial cages for the delivery of mRNA into cells
Gene therapy is a promising approach for treating many genetic diseases, but it requires the delivery of nucleic acids within cells, a task that has proven rather challenging. The EU-funded LEVERAGE mRNA project is proposing the development of hollow containers made of proteins to deliver RNA molecules, mimicking the structure of viruses. Researchers will use lumazine synthase, a bacterial protein known to form symmetrical nanocompartments which can disassemble inside mammalian cells and release the encapsulated RNA molecules into the cytosol. The LEVERAGE mRNA approach offers a promising strategy for delivering mRNA molecules to replace missing or dysfunctional proteins, such as in enzyme replacement therapies, with obvious benefits for human health.
Objective
Nucleic acids are promising candidates for treating disease by stimulating, inhibiting, or replacing other nucleic acids or proteins inside of eukaryotic cells—a process known as “gene therapy.” However, methods to efficiently and safely deliver genes into cells are still lacking. The problem is that nucleic acids are not cell permeant and degrade before reaching the cytosol. One way to transport oligonucleotides into cells is by packaging them into hollow containers made of proteins, a method that has been successfully hijacked by viruses for a long time.
Here, we propose to design and engineer an artificial proteinaceous container that (1) selectively encapsulates ribonucleic acids (RNAs) using a known RNA recognition tag and (2) delivers this RNA into the cytosol of mammalian cells. Protein engineering, which embodies both rational design and computational modeling, will be used to create the starting design of this artificial protein container. The initial design will be based on the protein lumazine synthase from the bacterial organism Aquifex aeolicus (AaLS), which forms small but highly symmetrical nanocompartments in bacteria and is very tolerant to genetic changes. To optimize this design, we will use directed evolution to induce an artificial selection pressure on a large population of distinct capsid variants, allowing us to obtain only the best-performing capsid variants: those that can enter and disassemble selectively inside of mammalian cells, thereby releasing the enclosed RNA molecules into the cytosol. New AaLS containers will be thoroughly characterized using cutting-edge technologies, such next-generation sequencing and cryo-electron microscopy.
The ultimate goal of LEVERAGE mRNA is to use the designed and evolved capsids to deliver messenger RNAs (mRNAs) into cells that encode missing or dysfunctional proteins, for example in enzyme replacement therapies. If successful, this action will have lasting positive impacts on human health.
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 biochemistry biomolecules nucleic acids
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-2018
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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.
8092 Zuerich
Switzerland
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.