Nature communications

Lipid nanoparticles designed to deliver mRNA outside the liver

Updated

Abstract

Lipid nanoparticle (LNP) systems with a bilayer lipid to ionizable lipid molar ratio of 4 demonstrate 90-100% mRNA encapsulation efficiencies and excellent transfection potencies in vitro.

  • prepared at specific ratios exhibit a liposomal structure with a solid core and aqueous interior.
  • These liposomal LNPs have longer circulation lifetimes compared to those with Onpattro-like lipid compositions.
  • Enhanced transfection properties in extrahepatic tissues are observed in these liposomal LNPs.
  • The prolonged blood circulation is linked to reduced plasma protein adsorption.
  • Transfection competency is related to the release of the solid core containing mRNA as the endosomal pH decreases.

Simplified

Key numbers

90-100%
mRNA Encapsulation Efficiency
Encapsulation efficiency of LNP mRNA systems with bilayer to ionizable lipid ratio of 4.
15×
Circulation Lifetime Increase
Circulation half-life of liposomal compared to Onpattro-like formulations.

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Funding

Competing interests

Competing interests: P.R.C. has a financial interest in Acuitas Therapeutics and NanoVation Therapeutics as well as being Chair of NanoVation Therapeutics. D.W. is an employee of NanoVation Therapeutics. M.H.Y.C hold equity in NanoVation Therapeutics. Inc. The remaining authors declare no competing interests.
PubMed

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