Possible Mechanisms of mRNA-LNP Degradation: A Comprehensive Review

Area of Science:

• Biotechnology
• Pharmaceutical Sciences
• Drug Delivery

Background:

• Messenger RNA-lipid nanoparticle (mRNA-LNP) formulations are a significant advancement in prophylactic and therapeutic applications.
• The inherent instability of mRNA-LNP products necessitates stringent ultra-cold chain storage, limiting global distribution.

Purpose of the Study:

• To comprehensively review the physicochemical factors contributing to mRNA-LNP instability.
• To elucidate the molecular degradation mechanisms affecting mRNA and lipid nanoparticle components.
• To summarize current stabilization strategies and analytical detection methods for mRNA-LNP products.

Main Methods:

• Literature review focusing on physicochemical instability factors (temperature, pH, light, oxidation, aggregation, shear stress, humidity).
• Analysis of molecular degradation pathways impacting mRNA and LNP integrity.
• Compilation of reported stabilization techniques and analytical quantification methods.

Main Results:

• Identified key physicochemical factors that compromise mRNA-LNP integrity.
• Detailed the molecular mechanisms leading to structural and functional deterioration.
• Summarized diverse strategies for enhancing mRNA-LNP stability and methods for degradation assessment.

Conclusions:

• Understanding mRNA-LNP instability drivers is critical for maintaining product efficacy and safety.
• Effective stabilization strategies and analytical tools are essential for advancing nucleic acid-based therapeutics.
• Overcoming stability challenges will facilitate broader application and distribution of mRNA-LNP drug products.