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Related Experiment Video

Updated: Jan 7, 2026

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
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Biomimetic engineering peptidyl-based vehicles for efficient mRNA delivery.

Yu Li1, Di Wang2, Jihong Li2

  • 1Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, 100071, China; New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, China.

Biomaterials
|December 26, 2025
PubMed
Summary

Researchers developed H3M1-5, a novel peptide-based vehicle for mRNA delivery. This biomimetic platform shows promise for creating safe and effective mRNA vaccines with reduced inflammation compared to lipid nanoparticles.

Keywords:
Endogenous proteinPeptidyl-based vehicleVaccinemRNA delivery

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Area of Science:

  • Biotechnology
  • Vaccine Development
  • Protein Engineering

Background:

  • Antigen-encoding mRNA vaccines offer therapeutic potential but face challenges with existing delivery systems like lipid nanoparticles (LNPs) regarding reactogenicity and tolerability.
  • Developing novel, safe, and effective mRNA delivery platforms is crucial for clinical translation.

Purpose of the Study:

  • To engineer a novel, single-component, peptidyl-based vehicle (H3M1-5) for efficient and safe mRNA delivery.
  • To evaluate the biocompatibility, delivery efficiency, and immunogenicity of the H3M1-5 platform.
  • To assess the efficacy of H3M1-5 mediated mRNA vaccines in disease models.

Main Methods:

  • Screening and modification of functionalized motifs from an endogenous retrovirus-like protein to create the H3M1-5 vehicle.
  • In vitro and in vivo evaluation of H3M1-5 for delivering linear mRNA, circular mRNA, and plasmid DNA.
  • Assessment of immune responses and protective efficacy using mRNA vaccines encoding M1R (orthopoxvirus) and OVA (melanoma) in mouse models.

Main Results:

  • H3M1-5 demonstrated efficient mRNA and DNA delivery comparable to commercial reagents, with good biocompatibility and modularity.
  • Peptidyl-based mRNA vaccines facilitated germinal center responses and elicited robust immune responses.
  • H3M1-5@M1R mRNA provided significant protection against lethal orthopoxvirus challenge, while H3M1-5@OVA mRNA delayed melanoma growth.
  • Unlike LNP formulations, H3M1-5 vaccines showed no detectable pro-inflammatory response and restricted transgene expression to the injection site.

Conclusions:

  • H3M1-5 represents a promising, simple, and biomimetic peptidyl-based vehicle for mRNA vaccine delivery.
  • This platform offers a favorable safety profile with reduced reactogenicity compared to LNPs.
  • The H3M1-5 platform holds potential for developing next-generation mRNA vaccines and therapeutics.