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CLOCK-Lipo
- Development stage
- Preclinical
- Lead developer
- Huazhong University of Science and Technology
- Modality
- Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
CLOCK-Lipo is a biomimetic lipid nanoparticle system designed for the treatment of sepsis-induced immunosuppression. It is fabricated by fusing cell membranes from lipopolysaccharide (LPS)-stimulated macrophages and erythrocytes co-extruded with siRNA targeting nuclear receptor subfamily 1 group D member 1 (siRNA-NR1D1) with cardiolipin-enriched vesicles using DNA zippers. CLOCK-Lipo targets macrophages and delivers siRNA-NR1D1 to knock down NR1D1 expression, which is persistently upregulated during sepsis. This knockdown restores the expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a direct target of NR1D1 that is critical for immune cell activation and cytokine production, thereby restoring circadian rhythmicity and modulating macrophage polarization to improve survival rates in sepsis.
- Other names
- siRNA-NR1D1-loaded biomimetic nanoparticlessiRNA-NR-1D1-loaded biomimetic nanoparticlessiRNA-NR 1D1-loaded biomimetic nanoparticles
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