Archaea-inspired deoxyribonuclease I liposomes prevent multiple organ dysfunction in sepsis.

Summary

A red blood cell membrane–fused, methyl-branched liposomal DNase I formulation efficiently degraded NETs and cfDNA, prolonged circulation, reprogrammed innate immune activation, and prevented organ dysfunction in septic mice. This platform supports NETs/cfDNA clearance as a tractable therapeutic axis in sepsis.

Key Findings

• DNase I/Rm-Lipo efficiently cleared NETs and cfDNA in activated neutrophils.
• The formulation prolonged DNase I circulation time and suppressed neutrophil activation while modulating macrophage polarization.
• In septic mice, DNase I/Rm-Lipo mitigated inflammation and prevented multiple organ dysfunction.

Clinical Implications

Supports development of DNase-based adjuncts for sepsis, with potential patient selection using cfDNA/NETs biomarkers and combination with standard source control and antibiotics.

Limitations

• Preclinical study without human safety or efficacy data.
• Details of sepsis model standardization, dose–response, and long-term immunogenicity are not provided in the abstract.

Future Directions

Translate to large-animal models, define dosing and immunogenicity, and design early-phase trials with NETs/cfDNA biomarkers for enrichment.