Polypeptide-engineered lipid nanoparticles for mRNA delivery with limited immunogenicity

May 29, 2026Nature communications

Protein-designed lipid nanoparticles for mRNA delivery with low immune response

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Abstract

pDLS-LNPs loaded with SARS-CoV-2 spike mRNA achieve superior mRNA delivery compared to the clinically approved BNT162b2 formulation.

  • Hydrophilic, nonionic, and biodegradable poly(D, L-serine) lipids may serve as effective alternatives to polyethylene glycol lipids in lipid nanoparticle formulations.
  • Systematic structural screening identifies optimal architectures that result in colloidally stable pDLS-LNPs with high mRNA encapsulation and transfection efficiency.
  • pDLS-LNPs elicit robust cellular and humoral immune responses in mice without causing systemic toxicity.
  • Unlike PEG-based nanoparticles, repeated dosing with pDLS-LNPs triggers minimal anti-pDLS IgM production.
  • pDLS-LNPs maintain stability under frozen storage for over 6 months.

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