Engineering safer, smarter cells – what the EC is really asking for in the HORIZON-HLTH-2025-01-TOOL-01 call
20th June 2025 at 2:45 pm
The Horizon Europe call HORIZON-HLTH-2025-01-TOOL-01 is not just about advancing cell therapies; it’s about making them safer, programmable and clinically actionable through genomic engineering. With a growing demand for off-the-shelf and personalised therapeutic solutions, the European Commission (EC) is asking researchers, biotech, pharma and other companies to go beyond innovation hype and deliver designs that are grounded in therapeutic benefit, technical rigour and regulatory foresight. In this blog, we unpack the EC’s expectations and highlight what to prioritise when preparing your Horizon Europe Health proposals.
1. A new generation of cell therapy: customisable, controllable and compliant
This call supports next-gen cell therapy that’s engineered from the gene level up. Unlike traditional approaches, applicants must design human allogeneic cells with intrinsic therapeutic functions enhanced by synthetic biology, genome or epigenome editing. Key EC expectations include:
- Customised cells with programmable therapeutic properties
- Genomic switches and control systems for precision delivery and regulation
- Use of advanced tools like CAD platforms in design-build-test workflows
- Exclusion of drug-loaded cells (the therapeutic effect must be endogenous)
Pro tip: Clearly explain your “sense-and-respond” logic or other control features. The EC wants to see cell behaviours that are not only enhanced but also measurable, safe and tunable.
2. Theranostic logic and synthetic circuits are central
The EC expects engineered cells to behave like miniature programmable units, able to detect, act and respond dynamically. This means your design should integrate:
- Synthetic genetic circuits acting as on/off switches
- Gene control at transcriptional, translational or post-translational levels, or other approaches to generate on-off switches
- “Theranostic” features that link therapy with embedded diagnostic function
Pro tip: Do not just mention synthetic biology or epigenetic editing. Show how your approach enables smart, targeted functions that generate customised cells with improved therapeutic features.
3. Targeted therapeutic areas: choose one and justify deeply
Proposals must focus on one therapeutic area only, selected from a defined list. Any disease, dysfunction or health impairment may be selected as therapeutic area. Be specific about:
- The unmet need in the selected area
- Why your cell engineering approach offers a meaningful advantage
- Preclinical models that reflect real clinical complexity
Pro tip: Use disease-area data to justify both therapeutic relevance and eventual patient benefit.
4. Safety and regulatory alignment are not optional
To stay competitive, proposals should show early alignment with regulatory pathways in the road to clinical translation. That includes:
- Engaging with regulatory authorities and HTA bodies during the project
- Addressing safety in-vitro, ex-vivo and in-vivo, including in appropriate pre-clinical models
- Demonstrating the feasibility of the proposed cell-based therapy in first in-human studies, if possible.
Pro tip: Outline how your safety, efficacy and control systems will meet future clinical and regulatory requirements and not just technical feasibility.
5. Preparing for clinical relevance and building strong consortia
This topic is designed for projects nearing clinical readiness, and proposals should reflect that maturity from the outset. Under this topic, clinical studies are expected. What to include:
- A plan for first-in-human studies using the dedicated clinical study annex
- A roadmap for regulatory interaction, including qualification of test methods
- SMEs, which are strongly encouraged to participate
Pro tip: Design your consortium with the clinical pathway in mind. Bring together scientific excellence, SME innovation, and regulatory insight to demonstrate end-to-end feasibility.
Changes in the new Part B template
Please note the following when getting started with your proposal preparation: As of the latest updates to the Horizon Europe RIA/IA proposal template (Part B, v4.0 from December 2024), several noteworthy adjustments have been made. The guidance notes under Section 1.2 Methodology concerning the Do No Significant Harm (DNSH) principle and the technical robustness of AI have been removed. Additionally, the requirements on data management have been simplified: the dedicated Research Data Management chapter has been eliminated and, instead, a brief reference to the Data Management Plan (DMP) has been integrated under the Open science practices section, streamlining the treatment of research data. On a positive note, the template now includes a new, direct link to the EU’s sex and gender reference documentation, making it easier for applicants to ensure appropriate integration of sex/gender dimensions in their research. These changes reflect a simplification and targeted focus in the current template structure.
For more information or general advice on the call topic, please consult your National Contact Point.
Looking for proposal writing support from experts with biomedical experience?
Since our foundation, we have been collaborating with more than 1,000 organisations in Europe and beyond. At accelopment, we have been supporting consortia working at the forefront of cell engineering, genomic innovation and translational medicine for many years. Our track record includes Horizon Health RIAs such as GENEGUT and VANGUARD, and Innovative Training Networks like CLICKGENE and NATURE-ETN. These fields and are in addition to our other successful Research and Innovation Actions (RIAs and IAs) HORIZON Health projects EXPOSIM, EU PAL-COPD, GLIOMATCH, COVend and MyPath. We are also actively involved in Horizon 2020 Health projects still running such as EXIMIOUS. Additionally, our support extends to many more health-focused ITNS, including MITGEST and MobiliTraIN, as well as Pathfinder-Open projects related to health, such as POLINA and BoneOscopy
From strategic planning to full proposal development and project implementation, we work closely with researchers, companies and institutions to navigate the EU funding landscape. Whether you’re aiming for success in a Cluster 1 Health call or enhancing your project’s communication, dissemination and impact strategy, our team is ready to support you. Let’s connect and explore how we can help maximise your Horizon Europe opportunities.