Project description
Gene therapy to improve lung transplant outcomes
Lung transplantation remains the definitive treatment for individuals with end-stage pulmonary disease. However, post-transplant survival rates are low due to immune rejection and the complications caused by reperfusion injury. Standard immunosuppressive treatments have demonstrated limited efficacy in preventing reperfusion injury, highlighting the need for alternative strategies. With the support of the Marie Skłodowska-Curie Actions programme, the LifeLUNG project proposes to precondition donor lungs before transplantation with a dual approach that combines ex vivo lung perfusion and gene therapy. Researchers will utilise advanced machine learning and deep sequencing to identify key immune and gene targets of reperfusion injury. LifeLUNG will develop advanced delivery vehicles to ensure specific genetic modulation of lung grafts.
Objective
Patient survival after lung transplantation (LTx) for end-stage pulmonary disease is poor (5-year survival rate of 59%) due to ischemia reperfusion injury (IRI) and graft rejection. No therapies are available to prevent IRI, and current immunosuppression causes toxicity and morbidity. Novel strategies are required that can mask the graft from the recipient’s immune system
The LifeLUNG initiative unites the critical building blocks available in Europe to advance towards a novel paradigm for LTx. Ex vivo lung perfusion (EVLP) is a clinically used platform to maintain active lung physiology outside the body, making pre-LTx organ engineering a reality. The project aims to advancing EVLP technology to enhance our understanding of transplant rejection through accessible models. By utilizing biobanks of lung biopsies from both clinical LTx cases and established animal models of IRI and rejection, LifeLUNG will apply advanced machine learning and AI-driven deep sequencing to identify key immune factors and gene targets. The latter will be targeted in LifeLUNG with gene therapeutic agents (GTAs) that can be delivered during EVLP to selectively modulate immune responses. Several delivery tools including adeno-associated viral vectors, virus-like particles and lipid nanoparticles, will be tailored to ensure precise and graft-specific gene modulation, enhancing the therapeutic potential for reducing IRI and preventing rejection. Also the efficient production strategies of these GTAs will be an integral part of LifeLUNG. In parallel, LifeLUNG will explore the economic and ethical paradigms of genetic modification of lung transplantation and reflect its implementation into the broader research and clinical framework.
The interdisciplinary nature of LifeLUNG will support the training of 15 doctoral candidates across clinical, academic, and industrial sectors, fostering collaboration and the development of transferable skills to advance the research objectives.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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)
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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-DN - HORIZON TMA MSCA Doctoral Networks
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(opens in new window) HORIZON-MSCA-2024-DN-01
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3000 Leuven
Belgium
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Participants (11)
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92150 SURESNES CEDEX
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1090 Wien
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72074 Tuebingen
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22100 Lund
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08028 BARCELONA
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51429 Bergisch Gladbach
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3001 Louvain
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WC1E 6BT London
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8000 Aarhus C
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08015 BARCELONA
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3584 CX Utrecht
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Partners (12)
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4051 Basel
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400 14 Goteborg
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151 85 Sodertaelje
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10801 New Rochelle
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8780 Oostrozebeke
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1120 Vienna
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2332 KG Leiden
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91190 Gif-Sur-Yvette
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08007 Barcelona
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08017 Barcelona
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Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
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3584 CS Utrecht
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Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
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75007 Paris
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