Oligonucleotides serve as one of the most promising classes of drug modality. However, attempts to establish a physicochemical evaluation platform of oligonucleotides have been limited. We have evaluated the higher-order structure and the thermodynamic stability of the thrombin-binding aptamer (TBA) and four modified TBAs with six pharmaceutical companies to establish harmonized physicochemical profiling platform for oligonucleotides. The relationship between the higher-order structure and the solution properties including solubility, viscosity, and stability, and its impact on the antithrombin activity were also investigated. Each instrumental analysis had a complementary role in investigating the higher-order structure of TBA and modified TBAs. The utility of each physicochemical characterization method during the preclinical developmental stages is discussed.
Learning Objectives:
Upon completion, participant will be able to comprehend overview of the physicochemical characterization of oligonucleotides.
Upon completion, participant will be able to understand impotance to consider available amount of oligonucleotides for their physicochemical evaluation.
Upon completion, participant will be able to understand impact of higher-order structure of oligonucleotides on their physicochemical properties
