Histidine Decapeptide‐Incorporating Lipid Nanoparticles with Low Ionizable Lipids Proportion for Efficient Small Interfering RNA Delivery

May 14, 2025Macromolecular bioscience

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

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Abstract

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

  • Lipid nanoparticles (LNPs) are essential for delivering (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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Key numbers

1.6×
Increase in Efficiency
LNP5H vs. conventional
27.72%
Ionizable Lipid Proportion
LNP5H composition
4 weeks
Storage Duration for Potency
LNP5H in 1% sucrose solution at -70 °C

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