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Title:
Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus | Nature Communications
Description:
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. In the context of increasing bacterial antibiotic-resistance, gene therapy that targets the immune system to clear infection is a major goal. Here the authors show a silicon based nanosystem that modulates the macrophage response in an in vivo model of Staphylococcal pneumonia.
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Keywords {🔍}
pubmed, fusogenic, mice, article, google, scholar, macrophages, infected, cas, sirna, fig, lungs, irf, cell, cells, post, infection, lipid, nps, pbs, peptide, crv, knockdown, nanoparticles, macrophage, delivery, lung, vivo, healthy, aureus, membrane, injected, inflammatory, particles, mouse, targeting, central, nature, gene, bacterial, control, uptake, psi, fusion, treatment, dii, showed, targeted, organs, injection,
Topics {✒️}
nature portfolio 2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[maleimide 2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy interest policies f-psi-cal nf-psi-cal privacy policy advertising fusogenic nature programmable melanoma-targeted radio-immunotherapy tak1-ikkbeta-irf5 signaling pathway research findings included woodhead publishing series 2-dimyristoyl-sn-glycero-3-phosphocholine nature 434 nature visible f-dii-crv accumulation reprints f-siirf5-crv nanoparticle constructs development dii-loaded f-psi nanoparticles phage library screen38 dii-loaded nf-psi nanoparticles calcein-loaded f-psi nanoparticles f4/80-af555 macrophage marker nanoporous silica-based protocells calcein-loaded nf-psi nanoparticles woodhead publishing agar-coated petri dishes fatal deep-tissue infection promote peg-mediated fusion61 f-siirf5-crv nano-therapeutic single-crystal silicon wafers generating multi-organ failure f4/80-af555 macrophage signals anti-inflammatory tissue regeneration research induces ifn-beta production macrophage-specific targeting yielded mai-tai laser hb downregulates anti-inflammatory cytokines antibiotic-resistant bacterial infections fluorescence-activated cell sorting final f-psi constructs antibiotic-loaded nanoparticles targeted hong-bo pang th1/th2 paradigm extended f-psi formulation fused reported oligonucleotide-loaded nanoplatforms permissions staphyloccocus aureus pneumonia
Questions {❓}
- Could silencing IRF5 improve healing of a myocardial infarct through the reprogramming of the macrophage population?
- Is RNAi dead?
- Th1/Th2 paradigm extended: macrophage polarization as an unappreciated pathogen-driven escape mechanism?
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description: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 systemâs 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. In the context of increasing bacterial antibiotic-resistance, gene therapy that targets the immune system to clear infection is a major goal. Here the authors show a silicon based nanosystem that modulates the macrophage response in an in vivo model of Staphylococcal pneumonia.
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headline:Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus
description: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 systemâs 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. In the context of increasing bacterial antibiotic-resistance, gene therapy that targets the immune system to clear infection is a major goal. Here the authors show a silicon based nanosystem that modulates the macrophage response in an in vivo model of Staphylococcal pneumonia.
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