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SYNTHETIC GENE CIRCUITS FOR CLOSED-LOOP THERAPY

Project description

Gene therapy platform could deliver therapy on demand

Genetics research has revealed many disease markers and processes and opened the door to gene therapies. Now, the EIC-funded SECURE project aims to create the world’s first self-adaptive gene therapy platform, delivering on-demand therapy with the potential for preventive therapy as well. The platform will activate synthetic gene circuits only in cells exhibiting disease-induced molecular stress, leveraging synthetic biology, AI and advanced disease modelling. The project will focus on vulnerable dopaminergic neurons in Parkinson’s disease as a test case and use midbrain organoids from human induced pluripotent stem cells to test selectivity, reversibility and safety. SECURE’s progress could pave the way to preventive, adaptive, lifelong gene therapy for many progressive and complex disorders.

Objective

"What if gene therapy could think, adapt, and act only when needed? SECURE sets out to create the world’s first self-adaptive gene therapy platform ‒ a transformative leap from today’s static interventions toward programmable, intelligent therapeutics. Rather than permanently active vectors, our approach uses synthetic gene circuits that remain dormant under healthy conditions and activate only in cells exhibiting disease-induced molecular stress. This ""on-demand"" precision therapy promises unprecedented safety, efficacy, and personalisation.
As a first-in-class application, SECURE targets Parkinson’s Disease (PD) by focusing on vulnerable dopaminergic neurons identified through stress markers such as AGTR1 expression, inflammation, and oxidative damage. Using AI-guided design, we will engineer AAV and bocavirus vectors tailored for efficient blood-brain barrier (BBB) transcytosis and neuron-specific targeting, guided by human receptor maps from neurotropic viruses.
Validation will rely exclusively on human iPSC-derived midbrain organoids ‒ including mosaic models combining healthy and PD genotypes ‒ to test selectivity, reversibility, and safety. A closed-loop development pipeline will be established, where data from single-cell transcriptomics, electrophysiology, and functional assays continually refine vector design through AI feedback.
By integrating synthetic biology, AI, and advanced disease modelling, SECURE pioneers a new therapeutic paradigm for neurodegeneration and potentially for multifactorial and hereditary diseases at large. If successful, it will mark the beginning of preventative, adaptive, and lifelong gene therapy for complex human disorders.
"

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-EIC - HORIZON EIC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) HORIZON-EIC-2025-PATHFINDEROPEN

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Coordinator

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Net EU contribution

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.

€ 448 437,50
Address
SEMINARSTRASSE 2
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 448 437,50

Participants (5)

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