马克和詹妮弗·利普舒尔茨精密免疫学研究所科研团队报道了抗炎脂质中作为肽体mRNA的抗菌肽向肺传递治疗多重耐药细菌性肺炎。2025年11月26日出版的《自然—生物技术》发表了这项成果。

研究团队通过将AMP转化为肽体形式，通过抗炎脂质纳米颗粒传递其mRNA构建物，将AMP与片段结晶结构域结合，激活先天免疫和cathelin结构域，以激活感染反应，从而提高AMP在肺部的性能。在多重耐药肺炎模型中，得分最高的设计优于美国食品和药物管理局批准的抗生素治疗，在减轻炎症的同时根除了代表性的耐多药细菌。作为mRNA多肽体递送到无主题肺的抗菌肽可根除多药耐药肺炎。

据了解，抗菌肽（AMPs）的功效受到递送和效力挑战的限制。

附：英文原文

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

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

Issue&Volume: 2025-11-26

Abstract: 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. Antimicrobial peptides delivered to mouse lung as mRNA peptibodies eradicate multidrug-resistant pneumonia.

DOI: 10.1038/s41587-025-02928-x

Source: https://www.nature.com/articles/s41587-025-02928-x