Project description
Navigating drugs into cancer cells
The specificity of drug delivery is paramount to avoiding toxicity and other drug-related side effects. However, shuttling therapeutic agents to specific cells or within cells remains a significant challenge. Funded by the European Research Council, the bioTARGET project proposes to develop a chemically controlled approach that will achieve specific intracellular delivery of therapeutics with molecular precision. The strategy relies on bioorthogonal chemistry that does not interfere with native biochemical processes. Researchers will design activatable ligands with spatial and temporal control features for the delivery and release of therapeutics within cells.
Objective
Bioorthogonal chemistries cross the boundaries between static chemical connectivity and the dynamic physiologic regulation of molecular state, enabling powerful tools for molecular control in complex biological environments. In combination with ligand-directed drug delivery, safe and selective chemical reactions that perform efficiently in vivo can fuel the design of new therapeutic strategies. Despite significant progress in the field of drug targeting, it remains challenging to shuttle therapeutic agents to the desired tissue, reaching the necessary cellular and even sub-cellular level, all while avoiding collateral damage. To engage this challenge, I aim to develop the concept of bioorthogonal cascade-targeting to direct the recognition, activation, and intracellular delivery of therapeutic constructs with molecular precision. We will develop next-level chemical tools for bioorthogonal bond-cleavage with exceptional reaction performance and the unique capability of tunable sequential release events (‘tandem release’). These innovations will enable us to design bioorthogonally activatable ligands for multiple therapeutic approaches that open new ground, most notably in escalating the complexity of (bio)chemical choreography. In particular, I propose cascade-processes, triggered by a single biocompatible click event, that can achieve: (i) the ‘bridging’ of non-internalizing cell-surface receptors to forward therapeutics into cells; (ii) the ‘hopping’ of drug conjugates from one target to another, or from one cell to another; and (iii) kinetically preprogrammed ‘escape’ of drugs from the endosomal compartment of cells entered via cascade-targeting. This will allow us to spatially and temporally control the movement and release of therapeutics in a (sub)cellular environment, and ultimately to establish bioorthogonal cascades as unique strategies that shift the paradigm of biologically controlled drug delivery.
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.
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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.1.1 - 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.
HORIZON-ERC - HORIZON ERC Grants
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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-2021-STG
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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.
1040 Wien
Austria
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.