MISSION & VISION
How LifeLUNG tackles unmet clinical needs and technology & knowledge gaps
Tackling unmet clinical needs
Common complications after lung transplantation are ischemia-reperfusion injury and primary graft dysfunction, and chronic organ rejection affects 50% of patients. Immunosuppressant therapy is associated with significant toxicity and vulnerability to infections. There is also an ongoing shortage of donor organs. New strategies are urgently needed to reduce the risk of lung transplant complications, an increase the pool of organs that are available for transplantation.
Innovation in LifeLUNG
LifeLUNG will develop gene therapies for donor lungs to improve their quality for transplantation and reduce the risk of rejection. The project will refine EVLP technology, leverage biobanks for gene target discovery, and use machine learning to identify immune factors linked to rejection. It will also develop gene modification methods and delivery tools tailored to the lung, scalable production of gene therapies, and obtaining understanding of economic and ethical insights throughout the research-to-clinic pipeline.
The power of co-creation
LifeLUNG will train 15 Doctoral Candidates (DCs) within a clinical, academic, and industrial network, to advance European leadership in lung transplantation. LifeLUNG is led by KU Leuven, home to UZ Leuven—one of Europe’s top lung transplant centers. Other partners are innovators and stakeholders in lung transplantation and gene therapy, from top research institutions, clinical centers, industry and non-profit organizations. Together they form a strong interdisciplinary network to advance lung transplantation science and practice.
SCIENTIFIC WORK PACKAGES
LifeLUNG research activities are organised in four work packages (WPs).
WP1 : Models
DC1, DC2, DC3, DC4
WP1 will develop advanced models to study lung transplantation, ischemia-reperfusion injury, and rejection, which can support the study of these complications and preclinical testing of gene therapy. New systems will include a mouse EVLP model (DC1) for in-lung gene editing, a long duration EVLP platform using negative pressure ventilation (DC2), isolated lobar perfusion of resected human lungs (DC3), and an organ-on-a-chip (model (DC4) simulating ischemia reperfusion injury. These models will evaluate gene therapeutic agents based on siRNA and CRISPR-Cas9, assessing delivery and silencing efficiency. Together, they provide a scalable, cost-effective pipeline for optimizing genetic interventions prior to clinical application.
WP2 : Omics & AI
DC1, DC5, DC6, DC7
WP2 aims to uncover cell-type-specific molecular mechanisms driving lung transplant rejection and ischemia-reperfusion injury using cutting-edge multi-omics and AI tools. Spatial transcriptomics, proteomics, and single-cell RNA sequencing will be applied to human and mouse models, leveraging rich biobank resources from four clinical partners. Novel target genes will be identified through detailed analysis of sequential lung biopsies and integrated into AI platforms to prioritize therapeutic candidates (DC1). T cell receptor sequencing will map adaptive immune responses, aiding in the prediction and treatment of rejection (DC6). Additional platforms like MACSima™ and RNASky™ will offer high-resolution spatial and molecular profiling (DC5, DC7).
WP3 : Delivery & Tools
DC8, DC9, DC10, DC11
WP3 focuses on developing innovative, efficient, and scalable tools for delivering gene therapeutic agents to lung tissue during ex vivo lung perfusion. DC9, DC10, and DC11 will optimize lipid nanoparticle (LNP)- and virus like particle (VLP)-based delivery systems for siRNA, mRNA, and CRISPR-Cas-based gene modulation, targeting key inflammatory or rejection targets. These systems aim to enhance targeting efficiency and specificity to lung cells of interest in lung endothelium and epithelium, both by vascular infusion and airway instillation. DC8 will scale VLP production using advanced bioreactor systems and digital optimization tools to ensure clinical-grade quality and cost-effectiveness.
WP4 : Ethical and
socio-economic implications
DC12, DC13, DC14, DC15
WP4 aims to ensure ethically responsible, economically viable, and socially acceptable clinical translation of gene therapy, guiding LifeLUNG innovations towards sustainable, real-world impact across diverse healthcare systems. It will explore views on genetic lung modification among lung donors, transplant recipients, clinicians, and the public, focusing on safety, consent, access, and fairness. DC13 and DC14 conduct qualitative and legal analyses on donor and recipient perspectives, including moral, legal, and societal concerns. DC12 evaluates health economics, modeling cost-effectiveness and equitable access. DC15 applies implementation science to overcome translational gaps from research to practice, identifying barriers and strategies for clinical integration.
WP5 : Training
All DCs
The LifeLUNG training programme is based on three main pillars:
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The individual training of each DC at their host institution, accessing relevant courses from their doctoral school and specialised training in the scientific skills required for their project
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Secondments, involving time spent at other LifeLUNG partners to gain research skills and knowledge, as well as experience of different work environments
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Network-wide training activities, including a series in-person training schools for all DCs, incorporating both scientific and transferable skills training, as well as online training activities.
WP6 : Exploitation, dissemination & communication
All DCs
WP6 organises the project activities to raise awareness of LifeLUNG among our target audiences and disseminate our results, increase public understanding of our research, and develop plans for exploitation and the continuation of collaboration after the project. Our DCs will contribute to dissemination and communication activities as part of their training. We will use social media and make a video. Results will be disseminated through publication in scientific journals, and at conferences including a specially organised LifeLUNG sympsium at the end of the project.
WP7 : Management & governance
All DCs
WP7 organises the project activities for DC recruitment, the overall project management and coordination, data management and ethics. The LifeLUNG coordination team is based at KU Leuven. The network is overseen by a Supervisory Board, with subcommittees for Recruitment, Training, and Dissemination and Exploitation. DCs will be represented in the project through their own DC committee.
