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On the Influence of Fabrication Methods and Materials for mRNA‐LNP Production: From Size and Morphology to Internal Structure and mRNA Delivery Performance In Vitro and In Vivo
How production methods and materials affect mRNA nanoparticle size, shape, structure, and delivery in lab and living systems
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Abstract
A cost-effective microfluidic setup for synthesizing mRNA lipid nanoparticles (LNPs) was developed.
- LNPs synthesized with the custom microfluidic device exhibit uniform structure and dense cores.
- Ethanol injection leads to broader size distributions and a more inhomogeneous internal structure in LNPs.
- Small angle X-ray scattering data suggest tighter interactions between mRNA and lipids in LNPs from the custom device compared to those from a commercial device.
- Polysarcosine (pSar)-modified LNPs demonstrate higher transfection efficiency associated with increased surface roughness compared to PEGylated LNPs.
- The manufacturing approach has a minor influence on mRNA expression in vivo.
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