Description du projet
Une solution innovante pour le développement d’anticorps monoclonaux à haute concentration
La solubilité des protéines représente un défi central dans le développement de formulations à haute concentration protéique d’anticorps monoclonaux (Acm) thérapeutiques. Le projet SWIRL, financé par l’UE, entend surmonter cet écueil en utilisant l’acide ribonucléique (ARN) comme partenaire d’interaction biologique des protéines. Les ligands d’ARN courts et à faible interaction (SWIRL) augmenteront la solubilité des protéines cibles, empêchant toute agrégation indésirable par le biais d’interactions spécifiques et de l’altération de la structure du solvant. Les principaux avantages des SWIRL résident dans leur caractère non immunogène et biodégradable. L’objectif du projet est de développer et de commercialiser une suite logicielle de calcul pour la conception de SWIRL qui améliorent la solubilité des Acm thérapeutiques sujets à l’agrégation dans un contexte biopharmaceutique.
Objectif
Usage of therapeutic monoclonal antibodies (mAbs) has over the past 20 years become one of the most powerful pharmacological strategies in the treatment of various types of cancer, cardiovascular diseases and autoimmune disorders. Importantly, a central challenge in developing the required high protein concentration formulations of mAb therapeutics is the issue of protein solubility. The current approaches for addressing this challenge typically involve using different osmolyte excipients such as salts, carbohydrates, amino acids or surfactants, but they suffer from various problems including insufficient activity, low specificity, allergenic reactivity and others. Clearly, there exists an unmet need for novel strategies to increase the solubility of mAbs in pharmaceutical formulations in an efficient, cost-effective, target-specific manner. We propose to address this challenge by exploiting one of the central biological interaction partners of proteins, the RNA molecules. Specifically, we will: 1) bring to a product stage a computational software suite for designing short, weakly interacting RNA ligands (SWIRLs) that improve the solubility of aggregation-prone mAb therapeutics in a sequence- specific manner, and 2) commercialize the software for usage in a biopharmaceutical context. The designed SWIRLs increase the solubility of target proteins and shield them from unwanted aggregation through weak, specific interactions and a simultaneous alteration of solvent structure. Moreover, a major advantage of using short, standard unmodified RNAs is that they are non-immunogenic and are degradable in the blood, which makes them a unique material for formulation development. Importantly, the sequence-specific design of SWIRLs for a particular target protein will be based on fundamental physicochemical principles of RNA-protein interactions, recently elucidated by us in the context of our ERC Starting Independent grant project.
Champ scientifique
- natural sciencescomputer and information sciencessoftware
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- natural sciencesbiological sciencesbiological behavioural sciencesethologybiological interactions
- natural sciencesbiological sciencesgeneticsRNA
Programme(s)
Régime de financement
ERC-POC - Proof of Concept GrantInstitution d’accueil
1010 Wien
Autriche