# Ambient-Stable mRNA Medicines: Emerging Paradigms in Dry and Solid-State Formulation

## TL;DR

This paper reviews strategies to make mRNA medicines stable at room temperature, enabling easier global distribution without cold storage.

## Contribution

The paper introduces emerging solid-state formulation methods and advanced design strategies for cold-chain-independent mRNA therapeutics.

## Key findings

- Solid-state stabilization methods like lyophilization and spray-freeze-drying improve mRNA stability.
- Self-amplifying RNA and nano-glass frameworks show promise for room-temperature stability.
- Combining molecular research with process development can enable durable mRNA medicines.

## Abstract

The medical field now uses mRNA therapeutics to deliver fast programmable treatment options through versatile vaccination platforms. The worldwide adoption of mRNA therapeutics faces a major obstacle because these molecules require extreme cold storage and transportation systems. mRNA stability establishes a fundamental scientific and industrial challenge which requires researchers to unite formulation design with process control and material engineering for cold-chain independence. Current knowledge about RNA hydrolysis and lipid oxidation and water-mediated degradation is combined with new methods for solid-state stabilization through lyophilization and spray-freeze-drying and thin-film technologies. Mechanism such as vitrification, water replacement and excipient RNA interactions are assessed to establish the fundamental chemical properties needed for extended product stability. Advanced mRNA development strategies are also examined, including self-amplifying and circular RNA structures and nano-glass and metal–organic frameworks and artificial intelligence-based predictive design for creating stable mRNA formulations at room temperature. This review examines manufacturing and regulatory and logistical obstacles which affect real-world implementation of mRNA therapeutics through assessments of production scale and product quality tests and packaging strength and tropical environment testing. The combination of research findings presents a path to develop mRNA medicines which maintains their effectiveness when stored at 25 °C or above, thus enabling worldwide access to RNA-based treatments. The development of mRNA into a durable therapeutic platform requires scientists to merge molecular research with process development and regulatory standardization.