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Optimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy

Author

Listed:
  • Xin Bai

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Qijing Chen

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Fengqiao Li

    (New Jersey Institute of Technology
    New Jersey Institute of Technology)

  • Yilong Teng

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Maoping Tang

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Jia Huang

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Xiaoyang Xu

    (New Jersey Institute of Technology
    New Jersey Institute of Technology)

  • Xue-Qing Zhang

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

Abstract

Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative “LOOP” platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08LOOP featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs. By incorporating mRNA encoding IL-11 single chain fragment variable (scFv), scFv@iLNP-HP08LOOP effectively delivers and secretes IL-11 scFv to the lungs of male mice, significantly inhibiting fibrosis. This formulation surpasses both inhaled and intravenously injected IL-11 scFv in inhibiting fibroblast activation and extracellular matrix deposition. The HP08LOOP system is also compatible with commercially available ALC0315 LNPs. Thus, the “LOOP” method presents a powerful platform for developing inhaled mRNA nanotherapeutics with potential for treating various respiratory diseases, including idiopathic pulmonary fibrosis.

Suggested Citation

  • Xin Bai & Qijing Chen & Fengqiao Li & Yilong Teng & Maoping Tang & Jia Huang & Xiaoyang Xu & Xue-Qing Zhang, 2024. "Optimized inhaled LNP formulation for enhanced treatment of idiopathic pulmonary fibrosis via mRNA-mediated antibody therapy," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51056-8
    DOI: 10.1038/s41467-024-51056-8
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    1. Yan Geng & Lin Li & Jie Yan & Kevin Liu & Aizhen Yang & Lin Zhang & Yingzhi Shen & Han Gao & Xuefeng Wu & Imre Noth & Yong Huang & Junling Liu & Xuemei Fan, 2022. "PEAR1 regulates expansion of activated fibroblasts and deposition of extracellular matrix in pulmonary fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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