Nature communications

Using charged lipid nanoparticles to improve inhaled mRNA vaccines for mucous membranes

Updated

Abstract

Inhaled (CAS-LNP) show enhanced stability during nebulization, enabling efficient pulmonary mRNA delivery.

  • CAS-LNPs maintain stability during nebulization, overcoming challenges associated with traditional lipid nanoparticles.
  • Efficient delivery of mRNA occurs in mice, dogs, and pigs, suggesting broad applicability across species.
  • Inhaled CAS-LNP effectively transfects dendritic cells, leading to strong immune responses both locally and systemically.
  • The CAS-LNP demonstrates potential as a vaccine against the SARS-CoV-2 Omicron variant and as a cancer vaccine targeting lung metastasis.
  • Design principles for nebulized lipid nanoparticles are outlined, which could facilitate future inhaled mRNA therapeutics.

Simplified

Key numbers

6.9×
Increase in mRNA Expression
Compared to SM102-LNP in mouse models.
15.5-fold
Total IgG Response Increase
Compared to SM102-LNP in serum after vaccination.
8.7-fold
Increase in OVA-specific T Cells
Compared to SM102-LNP in lung tissue.

Full Text

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Funding

Competing interests

X.L. and S.L. are inventors on a patent application (No. PCT/CN2023/130743) held by the Institute of Chemistry Chinese Academy of Sciences that covers the design and applications of CAS-LNP reported in this study. The remaining authors declare no competing interests.
PubMed

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