Project description
Efficient, versatile viral vectors to tackle complex genetic conditions
Gene therapies are promising for treating genetic disorders, but current methods face challenges. Adeno-associated viral (AAV) vectors are effective yet struggle to target certain cell types (muscle cells) and cannot carry large genes, often required for neuromuscular disorders. With the support of the Marie Skłodowska-Curie Actions programme, the TEHC project will tackle these challenges through two innovative approaches. Firstly, researchers will seek to enhance AAV targeting by integrating nanobodies into the viral capsid and refining them through directed evolution. This should help avoid immune responses. Secondly, researchers will pioneer the use of a bacteriophage-based vector capable of delivering large genes up to 171 kilobase pairs. If successful, TEHC will help improve gene delivery for complex genetic conditions.
Objective
Gene therapies are a fast becoming a realistic treatment for patients suffering from genetic disorders. To date, systemically applied in
vivo gene therapies exclusively rely on adeno-associated viral (AAV) vectors for gene delivery to affected cells. AAV vectors have many
features that make them successful gene delivery tools and through biomining and bioengineering efforts over the years, AAV
variants are able to transduce a number of clinically relevant targets. However, many cell types, including human muscle cells, are not
sufficiently transduced by existing viral vectors. Another challenge is the small genome size of AAV vectors, which is frequently a
problem for neuromuscular disorders where affected genes are larger than in other types of disorders. In the light of these challenges,
we are proposing to tackle new avenues for viral vector engineering in two separate, but related, objectives. Objective one is a new
way of viral vector re-targeting through incorporation of single domain antibodies (nanobodies) followed by a directed evolution
affinity maturation step. This approach of adds value to an already published method and should create a capsid-nanobody fusion
that is fit for purpose and potentially also has benefits regarding the evasion of pre-existing antibodies and improved packaging. The
second and more ambitious objective of our proposal consists of the adoption of a novel bacteriophage-based viral vector capable of
transducing mammalian cells and delivering up to 171 kilo base pairs of DNA. We are proposing to couple this new vector system
with our experience in capsid bioengineering and gene therapy, which has not been done before. For this objective, we propose to
incorporate antibody-derived targeting molecules such as nanobodies and single-chain variable fragments to highly protruding fibre
proteins on the bacteriophage surface and create cell type-specific viral vectors capable of delivering large genes, i.e. human
dystrophin.
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 genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics genomes
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-PF-01
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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.
75654 Paris
France
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.