Properties governing dry-state stability of RNA in amorphous sugar formulations

Abstract Formulation with non-crystalline amorphous solids, is a common strategy employed in nature for organisms to protect themselves from desiccation. These organisms typically accumulate high levels of disaccharides, such as trehalose, to achieve these amorphous states. These strategies have pre...

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Bibliographic Details
Main Authors: Tyler J. Gonzalez, Thomas C. Boothby
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Materials
Online Access:https://doi.org/10.1038/s43246-025-00850-y
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Summary:Abstract Formulation with non-crystalline amorphous solids, is a common strategy employed in nature for organisms to protect themselves from desiccation. These organisms typically accumulate high levels of disaccharides, such as trehalose, to achieve these amorphous states. These strategies have previously been co-opted for the stabilization of protein-based therapeutics, however, the applicability of amorphous sugars in the stabilization of RNA has not been fully explored. Here, we show that disaccharides improve stability of dry RNA up to a threshold, past which degradation occurs. This degradation is correlated with the water mass of dry samples as well as the dynamics of solid-state crystallization. Reducing water content and accelerating the transition from an amorphous to crystalline state increases RNA protection. Our results demonstrate that amorphous sugars are a cost-effective and efficient means of stabilizing RNA in a dry state outside of the cold-chain. Furthermore, we identify material properties of these dry materials that modulate the stability of embedded RNA.
ISSN:2662-4443