Project description
A novel synthetic virus for targeted gene delivery
The ability of viruses to infect, enter and replicate within cells has attracted great interest in the field of gene therapy. The EU-funded GENESHUTTLE project aims to create synthetic virus-like structures that carry genetic information of interest and recapitulate the properties of natural viruses. Researchers will employ DNA origami to ensure correct nucleic acid folding, while the generated particles will be able to interact with target membranes, trigger internalisation yet avoid uncontrolled autonomous replication. The GENESHUTTLE delivery system will constitute significant advancement to current approaches and is expected to find immediate applications in research and medicine.
Objective
Using rational design with DNA origami, we propose to create synthetic virus-like assemblies capable of accomplishing cell-invading and gene expression functionalities known so far only from natural viruses. We envision these assemblies to be useful for studying and testing viral import mechanisms, and also for gene delivery, enabling fundamental studies and potential medical applications. The objectives include selecting and invading a target cell type, systematically solving the challenges of endosomal escape and nuclear delivery, and inducing the expression of user-defined genetic information in the nucleus. To achieve these objectives, we will recreate and experimentally test mechanisms believed to be used by viruses, including receptor-mediated endocytosis, stimulus-dependent lipid membrane penetration, membrane fusion, active cytosolic transport, and nuclear import. We foresee building synthetic shells carrying genetic information stored in nucleic acids, which we refer to as the “gene shuttle”. The particles will optionally include a membrane envelope and user-defined surface features to mediate receptor-ligand interactions with cell membranes, and they will be capable of stimulus-dependent conformational changes to trigger membrane fusion or membrane penetration. They will shed structural elements on the path to the nucleus, similar to viruses. In addition to delivering genes for fluorescent markers, as a proof of concept demonstration we plan to use the gene shuttle to deliver the genetic information for expressing chimeric antigen receptors (CAR) in a T cell line, which promises to be of use in cancer immunotherapy. The project promises to yield a gene delivery system with capabilities beyond current synthetic vectors, which struggle to overcome the many cellular barriers to deliver and express genetic cargo. For safety reasons, the gene shuttle will by design be unable to assemble in the context of a cell to prevent uncontrolled autonomous replication.
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 microbiology virology
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
ERC-ADG - Advanced Grant
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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) ERC-2020-ADG
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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.
80333 Muenchen
Germany
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.