Approach

The complementary expertise of the partners spans the entire development track from nanoparticle design via Good Manufacturing Practice (GMP)-based production to clinical expertise.

Design
Production
Safety & Effifacy
Clincal Study

Design

EXPERT will design modular nanocarriers consisting of an mRNA payload, nanocarriers materials and, where applicable, a targeting ligand. The mRNA payload is a fragile molecule that bears the therapeutic activity. It can easily be destroyed by enzymes and has difficulties in reaching the site of activity. Therefore, the consortium will investigate the use materials to protect and deliver the mRNA, including established, emerging and exploratory components which could be suitable for GMP production.

Production

The modular nanocarriers will be manufactured through quality-by-design with excellent control over the physicochemical parameters, repeatability and scalability which is compatible with GMP production. To remove operator variability, enable seamless scale-up and allow for robust manipulation of a single variable per experiment, EXPERT will have microfluidics manufacture at all partners’ research sites. The well-characterised, reproducible nanocarriers will subsequently be validated for safety and efficacy in in vitro and in vivo experiments.

Safety & Efficacy

To evaluate the performance, EXPERT will investigate the tissue distribution, cellular targeting and cytoplasmic translocation of promising modular nanocarriers. A pre-clinical in vitro and in vivo safety assessment as well as in vivo checks of the mRNA nanomedicine translation will help to analyse the therapeutic efficacy in order to select the best mRNA formulation to be applied in a first clinical study.

Clinical Study

As proof-of-concept, the partners aim at a first in-man clinical study focusing on immunotherapy for metastatic triple-negative breast cancer, a subtype with high risk of relapse. In these patients, the primary lesion will be injected with the immune stimulatory mRNA nanomedicine while closely monitoring local and systemic adverse effects. After removing the tissue, the researchers will investigate immune cell recruitment as a surrogate marker of efficacy.