EXPERT: EXpanding Platforms for Efficacious mRNA Therapeutics

- Start: 01/09/2019
- End: 31/08/2024
- Budget: 14,93 M€

11 international partners from academia (Universitair Medisch Utrecht, Trinity College Dublin, Semmelweis Egyetem, Tel Aviv University, Karolinska Institutet), Research Organizations (Fundación CIDETEC, SINTEF)  and industry (AstraZeneca AB, eTheRNA, CYBERnano, EURICE) collaborate to develop a platform-based delivery system for mRNA nanomedicine to tackle the bottlenecks of mRNA therapy.

The complementary expertise of the partners spans the entire development track: Nanoparticle’s development using QbD, Good Manufacturing Practice (GMP) based production, Safety and Efficacy assessments and Regulatory compliance as well as clinical expertise.


The Project:

The European research project EXPERT addresses three of the most pressing challenges that have limited mRNA therapy from displaying its full potential:

- The ability to achieve functional target tissue delivery of mRNA by nanomedicine design.
- The capacity to efficiently reach target cell cytoplasm, the site of mRNA activity.
- The capability to circumvent adverse immune responses towards mRNA nanomedicines.

During the project timeframe, multiple mRNA encapsulating nanoparticle platforms will be tested in order to protect the mRNA, increase the target cellular uptake and reduce mRNA adverse immune-response. This will include the established lipid nanoparticles (LNPs) as well as emerging carriers such as cell penetrating peptides (CPP) and extracellular vesicles (EVs).

As proof-of-concept, the partners aim at a first clinical study focusing on immunotherapy for metastatic triple-negative breast cancer by using mRNA encapsulated into LNPs. The specific mRNAs would instruct patients’ cells to produce proteins which activate immune cells and liberate tumour antigens.

As a second field of application, EXPERT will investigate the use of mRNA for heart failure. Patients would receive a specific mRNA molecule helping to stimulate tissue regeneration in the heart without producing side effects elsewhere in the body.

Besides the production of the mRNA therapeutics, the project will investigate new pathways of delivering the mRNA payload to the targeted cells of activity through nanocarrier materials designed to protect the payload from being destroyed by the human body’s immune response. EXPERT will thus complement existing clinical studies with mRNA therapeutics which are predominantly ex-vivo trials inhibited by safety and targeting challenges.

The objectives of EXPERT can be summarized as follows:

- Development of mRNA Nanomedicines.
- Production of mRNA nanomedicines in a quality-by-design (QbD) approach. 
- Good Manufacturing Practice scale-up and clinical translation.
- First in-man clinical study with mRNA nanomedicines for immunotherapy.
- Investigation of mRNA nanomedicines for heart failure patients.

The off-the-shelf delivery system to be designed in EXPERT would substantially lower the costs of such treatments enabling the use of mRNAs as therapeutic interventions for more patients and different types of diseases.

CIDETEC'S role in the project:

CIDETEC Nanomedicine is in charge of the scale-up and clinical translation as well as GMP manufacturing of mRNA incapsulated into LNPs.

As well CIDETEC Nanomedicine collaborates on the development of analytical methods for the QC of produced materials.


The EXPERT project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 825828.