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<p>The efficacy of antimicrobial peptides (AMPs) is limited by challenges of delivery and potency. We enhance AMP performance in the lung by converting AMPs to a peptibody format that fuses AMPs with fragment crystallizable domains to activate innate immunity and cathelin domains for infection-responsive activation, with their mRNA constructs delivered by anti-inflammatory lipid nanoparticles. The highest-scoring design outperforms antibiotic therapy approved by the US Food and Drug Administration in multidrug-resistant pneumonia models, eradicating representative MDR bacteria while mitigating inflammation.</p>

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Antimicrobial peptide delivery to lung as peptibody mRNA in anti-inflammatory lipids treats multidrug-resistant bacterial pneumonia

  • 期刊论文

  • 发表日期：

    2025年11月26日

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  • Yonger Xue,
  • Xucheng Hou,
  • Siyu Wang,
  • Yuebao Zhang,
  • Yichen Zhong,
  • Diana D. Kang,
  • Chang Wang,
  • Haoyuan Li,
  • Changyue Yu,
  • Zhengwei Liu,
  • Meng Tian,
  • Dinglingge Cao,
  • Ya Ying Zheng,
  • Binbin Deng,
  • Pauline Hamon,
  • Miriam Merad,
  • Yizhou Dong

摘要

The efficacy of antimicrobial peptides (AMPs) is limited by challenges of delivery and potency. We enhance AMP performance in the lung by converting AMPs to a peptibody format that fuses AMPs with fragment crystallizable domains to activate innate immunity and cathelin domains for infection-responsive activation, with their mRNA constructs delivered by anti-inflammatory lipid nanoparticles. The highest-scoring design outperforms antibiotic therapy approved by the US Food and Drug Administration in multidrug-resistant pneumonia models, eradicating representative MDR bacteria while mitigating inflammation.