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Did you know that shaking or vortexing mRNA-lipid nanoparticles (LNPs) can compromise their integrity? A recent study, "Don’t shake it! Mechanical stress testing of mRNA-lipid nanoparticles", led by Andrea Allmendinger from the University of Freiburg, Germany, reveals that mechanical stress during handling and transport can lead to larger particle sizes, reduced nucleic acid encapsulation, and a decrease in the overall stability of these formulations.

Key Findings:

• Mechanical Stress Effects: Shaking or mechanical agitation of LNPs can damage the structural integrity of the lipid bilayers, affecting the encapsulation efficiency of mRNA and, in turn, reducing the overall stability of the formulation.
• Implications for RNA Therapeutics: These findings emphasize the need for optimized storage, transport, and handling conditions for LNP formulations to maintain their integrity. This is crucial to ensuring the mRNA vaccines and therapies we rely on remain effective.

Looking Ahead: The study calls for innovative strategies, like optimizing formulations and leveraging techniques such as lyophilization, to protect mRNA-LNPs during storage and transport. This can improve their stability, ensuring that cutting-edge mRNA-based therapeutics retain their full potential before reaching patients.

Read more: https://www.sciencedirect.com/science/article/pii/S0939641124000912?via%3Dihub

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When it comes to mRNA-lipid nanoparticles (LNPs), the more mRNA they carry doesn’t always mean better delivery. A recent study, "Transfection Potency of Lipid Nanoparticles Containing mRNA Depends on Relative Loading Levels," led by Pieter R. Cullis and Anna K. Blakney from the University of British Columbia, Canada, reveals an intriguing paradox—LNPs with higher mRNA loading levels actually show lower transfection efficiency, both in vitro and in vivo.

Key Findings:

• Optimal Loading is Key: The study highlights that there is an optimal balance in mRNA loading; both overloading and underloading the mRNA cargo can reduce the effectiveness of the nanoparticles in delivering the mRNA into target cells.
• Transfection Potency vs. Payload: This challenges the long-standing assumption that maximizing mRNA payload always enhances the therapeutic potential of LNPs.

Why It Matters: These findings shift the focus from simply maximizing mRNA content to finding the sweet spot that optimizes transfection efficiency. This research opens new pathways for designing next-generation LNPs that ensure potent and efficient delivery, paving the way for more effective mRNA-based therapies.

Read more: https://pubs.acs.org/doi/10.1021/acsami.4c20077

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