Lipid Nanoparticles with Histidine Peptides and Low Ionizable Lipids for Efficient Delivery of Small Interfering RNA

LNP5H, a lipid nanoparticle with a low ionizable lipid proportion of 27.72%, demonstrates a 1.6-fold increase in gene silencing efficiency compared to conventional lipid nanoparticles.

• Lipid nanoparticles (LNPs) are essential for delivering small interfering RNA (siRNA) and can have varying lipid compositions.
• Hydrophilic peptides cannot be encapsulated within LNPs formed by pipette or vortex mixing.
• The optimized LNP5 incorporates histidine decapeptide (His10) to enhance functionality without increasing ionizable lipid content.
• LNP5H maintains siRNA potency for 4 weeks when stored at -70 °C in a 1% sucrose solution.
• The fabrication methods used for LNP5H are fast and straightforward, potentially broadening applications for siRNA therapeutics.

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