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Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus

Author

Listed:
  • Byungji Kim

    (University of California, San Diego)

  • Hong-Bo Pang

    (Sanford Burnham Prebys Medical Discovery Institute
    University of Minnesota)

  • Jinyoung Kang

    (University of California, San Diego)

  • Ji-Ho Park

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Erkki Ruoslahti

    (Sanford Burnham Prebys Medical Discovery Institute
    University of California, Santa Barbara)

  • Michael J. Sailor

    (University of California, San Diego
    University of California, San Diego
    University of California, San Diego)

Abstract

The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system’s response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia.

Suggested Citation

  • Byungji Kim & Hong-Bo Pang & Jinyoung Kang & Ji-Ho Park & Erkki Ruoslahti & Michael J. Sailor, 2018. "Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04390-7
    DOI: 10.1038/s41467-018-04390-7
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