Target intelligence / Profile preview

Neutrophil extracellular trap DNA (NET DNA)

Target
NET DNA
Molecular classification
Nucleic acid, Damage-associated molecular pattern (DAMP)
01

Overview

Neutrophil extracellular trap (NET) DNA consists of extracellular chromatin fibers released by neutrophils to capture and kill pathogens. While essential for innate immunity, the persistence of these DNA scaffolds can trigger harmful inflammatory responses and tissue damage. In the context of cystic fibrosis, NET DNA significantly contributes to the high viscosity of pulmonary secretions, leading to airway obstruction. Furthermore, NET DNA serves as a scaffold for platelet aggregation and fibrin deposition, promoting immunothrombosis in cardiovascular diseases. It also plays a role in autoimmune diseases like systemic lupus erythematosus, where it acts as a source of autoantigens. Therapeutic intervention typically involves the use of recombinant human deoxyribonuclease I (rhDNase), which enzymatically cleaves the DNA backbone. This degradation reduces the physical viscosity of mucus and dismantles the pro-thrombotic and pro-inflammatory lattice. Emerging research also explores the role of NET DNA in shielding tumor cells from the immune system and promoting metastatic niche formation.

Other names
Extracellular DNAeDNANeutrophil extracellular trapsNETsCell-free DNAcfDNA
02

Mechanism of action

Enzymatic hydrolysis of phosphodiester bonds within the DNA backbone, leading to the degradation of the extracellular chromatin scaffold and reduction of fluid viscosity.

03

Biological functions

Innate immunityPathogen trappingInflammationCell death
04

Disease associations

Cystic fibrosisSystemic lupus erythematosusThrombosisCancer metastasisCOVID-19Rheumatoid arthritis
05

Safety considerations

Potential for increased risk of infection due to loss of pathogen-trapping capabilityTransient increase in inflammatory mediators upon rapid dissolution of NET structures
06

Interacting drugs

Dornase alfa

1 more in the full profile.

07

Biomarkers

Citrullinated histone H3 (H3Cit)Myeloperoxidase-DNA complexesCell-free DNA (cfDNA)

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