Rapid-Screening Differential Scanning Calorimetry for siRNA Duplex Thermal Analysis in Pharmaceutical Drug...

Rapid-screening differential scanning calorimetry (RS-DSC) is a novel technique that can be used for high-throughput, low-volume parallel thermal analysis of 24 samples at once. In this work, the utility of this instrumentation for the thermal analysis of therapeutic short interfering RNA (siRNA) duplexes is demonstrated in different contexts relevant to drug discovery and development, including formulation screening, analytical sample preparation, and simulated in vivo administration. Through these examples, it is showcased how this instrumentation can overcome limitations associated with conventional thermal analysis techniques to enable direct analysis in different media (without dilution), consumption of less material, and expanded throughput. These experiments demonstrate the versatility of thermal analysis techniques for therapeutic siRNA development and provide a roadmap for how this technique can be used in the development of chemistry, manufacturing, and controls (CMC) strategies.