Capillary Electrophoresis in RNA Therapeutics: Toward a Core Analytical Platform for Development, Release Testing, and Process Analytics

The rapid expansion of RNA therapeutics requires analytical methods that resolve molecular integrity, heterogeneity, and process-related impurities. Capillary electrophoresis (CE) provides direct RNA separation with low sample consumption and can be coupled with laser-induced fluorescence (LIF) or mass spectrometry (MS). This review assesses CE across RNA therapeutic development, release testing, and process analytics. We examine CE separation methods and platform formats for mRNA integrity and poly(A) tail analysis, size- and structure-related impurity profiling, circular RNA purity evaluation, RNA modification analysis by CE-MS, and aptamer discovery. We also discuss multi-capillary systems, microchip electrophoresis (MCE), automation, artificial intelligence (AI)-assisted data analysis, and bioprocess integration. CE is already highly useful for selected quality control tasks, especially mRNA integrity, poly(A) tail profiling, and circular RNA purity, but broader routine adoption requires improved sensitivity, standardization, method transfer, and regulatory acceptance.