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Extracellular double-stranded DNA (ecdsDNA) is a potent damage-associated molecular pattern (DAMP) released into the extracellular environment following cell death, tissue injury, or active processes such as NETosis (Nature Reviews Immunology, 2022). While typically cleared by endogenous nucleases, its accumulation is a hallmark of pathological states including autoimmune diseases, sepsis, and cancer (Journal of Clinical Investigation, 2019). In the extracellular space, ecdsDNA activates the innate immune system through receptors like Toll-like receptor 9 (TLR9) and the cGAS-STING pathway, driving inflammation (Science, 2015). In cystic fibrosis, high concentrations of ecdsDNA in the airways increase sputum viscosity, impairing lung function (New England Journal of Medicine, 1994). Therapeutic strategies involve enzymatic degradation using recombinant human DNase I (Dornase alfa) or the use of DNA-scavenging compounds to mitigate systemic inflammation and thrombosis (Blood, 2014).
Enzymatic hydrolysis of phosphodiester bonds in the DNA backbone, leading to the degradation of high-molecular-weight DNA into smaller, non-functional fragments (FDA, Pulmozyme Label).
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