Comparison of ionizable lipids for lipid nanoparticle mediated DNA delivery

Sep 11, 2024European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

Comparing charged fats for delivering DNA using lipid nanoparticles

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Abstract

Efficient transgene expression was achieved with a minimum amount of 1 pg DNA per initially plated cells.

  • Lipid nanoparticles (LNPs) are effective for RNA-based gene delivery and may also be promising for DNA delivery in gene replacement therapies.
  • The study evaluated different ionizable lipids (DLin-MC3-DMA, SM-102, and ALC-0315) for their impact on DNA expression plasmid delivery.
  • At an optimized N/P ratio of 6, DNA-LNPs exhibited small, spherical, and monodisperse characteristics with anionic ζ-potential.
  • Zebrafish studies indicated that selected DNA-LNPs achieved prolonged circulation in blood and reduced clearance by macrophages.
  • In wildtype mice, DNA-LNPs incorporating ALC-0315 showed superior transfection efficiency compared to other lipid types.

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Full Text

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