Quality assessment of LNP-RNA therapeutics with orthogonal analytical techniques

The availability of analytical methods for the characterization of lipid nanoparticles (LNPs) for in-vivo intracellular delivery of nucleic acids is critical for the fast development of innovative RNA therapies. In this study, analytical protocols to measure (i) chemical composition, (ii) drug loading, (iii) particle size, concentration, and stability as well as (iv) structure and morphology were evaluated and compared based on a comprehensive characterization strategy linking key physical and chemical properties to in-vitro efficacy and toxicity. Furthermore, the measurement protocols were assessed either by testing the reproducibility and robustness of the same technique in different laboratories, or by a correlative approach, comparing measurement results of the same attribute with orthogonal techniques. The characterization strategy and the analytical measurements described here will have an important role during formulation development and in determining robust quality attributes ultimately supporting the quality assessment of these innovative RNA therapeutics.

PAROT Jeremie;  MĖHN Dóra;  JANKEVICS Hanna;  MARKOVA Natalia;  CARBONI Michele;  OLAISEN Camilla;  HOEL Andrea;  SIGFUSDOTTIR Margret;  MEIER Florian;  DREXEL Roland;  VELLA Gabriele;  MCDONAGH Birgitte;  HANSEN Terkel;  BUI Huong;  KLINKENBERG Geir;  VISNES Torkild;  GIORIA Sabrina;  URBAN LOPEZ Patricia;  PRINA-MELLO Adriele;  BORGOS Sven Even;  CAPUTO Fanny;  CALZOLAI Luigi; 

2024-06-21

ELSEVIER

JRC136915

0168-3659 (online),   

https://www.sciencedirect.com/science/article/pii/S0168365924000506,    https://publications.jrc.ec.europa.eu/repository/handle/JRC136915,   

10.1016/j.jconrel.2024.01.037 (online),