Descripción del proyecto
Una técnica innovadora para el desarrollo de anticuerpos monoclonales de alta concentración
La cuestión de la solubilidad de las proteínas plantea un reto fundamental en el desarrollo de formulaciones de alta concentración proteica para tratamientos de anticuerpos monoclonales (AcM). El equipo del proyecto SWIRL, financiado con fondos europeos, aborda este obstáculo aprovechando el ácido ribonucleico (ARN) como compañero de las proteínas en la interacción biológica. Los ligandos de ARN cortos y de interacción débil (SWIRL, por sus siglas en inglés) aumentarán la solubilidad de las proteínas diana, lo que impide la agregación no deseada mediante interacciones específicas y la alteración de la estructura del disolvente. La gran ventaja de los SWIRL es que no son inmunógenos y son biodegradables. El objetivo del proyecto es desarrollar y comercializar un conjunto de programas informáticos para el diseño de SWIRL que mejoren la solubilidad de los tratamientos de AcM propensos a la agregación en un contexto biofarmacéutico.
Objetivo
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.
Ámbito científico
- natural sciencescomputer and information sciencessoftware
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- natural sciencesbiological sciencesbiological behavioural sciencesethologybiological interactions
- natural sciencesbiological sciencesgeneticsRNA
Programa(s)
Régimen de financiación
ERC-POC - Proof of Concept GrantInstitución de acogida
1010 Wien
Austria