Biomaterials

Targeted delivery of optimized mRNA nanoparticles to lymph nodes for COVID-19 vaccination

Updated

Abstract

The peptide-nanocomplex demonstrated stable particle formation under 200 nm and retained mRNA expression for up to 7 days in vivo.

  • Lipid nanoparticles (LNPs) often accumulate in the liver and show transient protein expression, which can limit their effectiveness.
  • The developed peptide-nanocomplex is composed of three functional peptides, including an RNA-binding peptide, charge-modulating polyglutamic acid, and an APC-targeting cell-penetrating peptide with a new immune cell-binding motif.
  • The peptide-nanocomplex remained localized at the injection site and effectively drained to the lymph nodes, unlike LNPs.
  • Mice immunized with SARS-CoV-2 spike mRNA using the peptide-nanocomplex showed robust neutralizing antibody titers comparable to those from LNPs.
  • The peptide-nanocomplex induced significantly higher CD8+ T cell responses than LNPs.
  • No toxicity was observed in vivo after daily injections for two weeks at doses up to 200 times higher than safe levels.

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Full Text

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Funding

Competing interests

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoon Jeong Park reports financial support was provided by Korea National Institute of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
PubMed

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