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Circulating cell-free DNA (cfDNA) refers to fragments of DNA found in the bloodstream and other body fluids, released from cells through processes such as apoptosis, necrosis, and active secretion, including the formation of neutrophil extracellular traps (NETs) [1.1.4, 1.4.1]. In healthy individuals, cfDNA levels are low and primarily derived from hematopoietic cells, but they increase significantly in pathological states like cancer, sepsis, and autoimmune diseases [1.1.2, 1.4.4]. cfDNA acts as a damage-associated molecular pattern (DAMP), activating the innate immune system through receptors like Toll-like receptor 9 (TLR9) and the cGAS-STING pathway, which can lead to chronic inflammation and tissue damage [1.4.1, 1.4.2]. In oncology, a subset known as circulating tumor DNA (ctDNA) serves as a critical biomarker for liquid biopsies, allowing for non-invasive monitoring of tumor mutations, treatment response, and minimal residual disease [1.2.2, 1.5.3]. Therapeutic targeting of cfDNA involves the use of deoxyribonucleases (DNases), such as Dornase alfa, which enzymatically degrade the DNA to reduce its pro-inflammatory and pro-thrombotic effects or to decrease the viscosity of DNA-rich secretions in conditions like cystic fibrosis and COVID-19 [1.3.1, 1.3.3, 1.3.4].
Enzymatic degradation of extracellular DNA fragments to reduce inflammation, thrombosis, and fluid viscosity.
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