RNA - Genetherapys
Spoke 9 - Competence Center

PROGRAM

Spoke 9 operates along short and long-term goals.
Short-term goals include leveraging its current expertise in regulatory sciences, by aligning them with the European Medicines Agency (EMA) and the American Food and Drug Administration (FDA) according to guidelines on bioanalytical method validation. We will develop and optimize standard analytical techniques, specifically Liquid Chromatography with tandem mass spectrometry (LC-MS/MS), for quantifying and understanding the biodistribution of RNA therapeutics. Such goals will be applied in clinical and preclinical distribution studies.
Additionally, we will utilize research from vertical Spokes to identify biomarkers suitable for verifying the activity of the RNA drug.

Long-term goals include testing and optimizing innovative concepts to expedite preclinical studies. This involves combining current steps required for ADMET profile studies with new protocols tailored for RNA drug development, based on a novel rational flow. The Competence Center for RNA drug pharmacology will integrate these novel concepts into the research program, creating new protocols accepted by regulatory agencies, where innovative biomarkers, combined with reporter systems, are suitable for in vivo imaging. These protocols aim to consolidate pharmacokinetics and pharmacodynamics studies into a single step, significantly improving sensitivity, reproducibility, and accuracy of results. Simultaneously, there will be a substantial reduction in the number of animals euthanized, aligning with the Replacement, Reduction, and Refinement principles (3Rs).

Spoke 9


SPOKE FLAGSHIPS

Enabling technologies for RNA drug discovery & development

  • Adapting existing technologies under the current regulatory framework.
  • Creating novel technologies to expedite RNA drug development.
  • Validating protocols for regulatory compliance.

CROSS-SPOKE ACTIVITIES

Spoke 9 works in close collaboration with the vertical Spokes 1, 2, 3, 4, and 5. These collaborations will guide the design of Pharmacokinetic (PK), Pharmacodynamic (PD), and Toxicokinetic (Tox) studies for the preclinical dossier while actively participating in the development of RNA drugs for the most promising agents identified by the National Center. The collaboration with the horizontal Spoke 6 will assess the PK, PD, and Tox impact of chemical modifications to drugs and will offer the delivery tools developed by Spoke 8. As an integral component of the project, Spoke 7 follows and ensures each step in the data management and analysis, including the application of Artificial Intelligence (AI) for unsupervised methodologies in detecting reporter activity through imaging.

The support of affiliated companies with Spoke 9 is crucial for creating scalable protocols for industrial use. Their support will allow for the development of efficient imaging tools, conducting quality assessments, initiating studies at locations that follow Principles of Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), and facilitating the translation of research products into standard and applicable technologies for RNA drug development.

Public-private partnerships are key to the success of Spoke 9, as collaboration with affiliated companies is indispensable for achieving the objectives of all Work Packages. Notably, the collaboration with Dompé Pharmaceuticals focuses on RNA vaccine immunotoxicology to develop new methods and in vivo models for immuno-toxicological evaluations, as well as GLP toxicological studies. Collaboration with the Chiesi Group centers on defining technologies for studying RNA drug distribution, with a specific emphasis on translating dosage studies conducted in laboratory animals into doses for human use. Eurofins Biolabs, as a global leader in testing and research services, supports research on optimizing current analytical procedures and exploring innovative methodologies. Antares Vision contributes to designing quality control methodologies and provides smart data and tools for the digitalization of the process. Throughout the three-year program, Spoke 9 is expected to engage with a majority of the companies currently present in the National Center, particularly for establishing technology transfer operations at the national and international levels.