Extracellular nucleic acids (eNA)

Extracellular nucleic acids (eNAs), comprising cell-free DNA (cfDNA) and RNA (cfRNA), are genetic materials released into the extracellular environment during cell death or through active processes like the formation of Neutrophil Extracellular Traps (NETs) [PMID: 31435341]. While present at low levels in healthy states, their concentration increases significantly during tissue injury, infection, and malignancy, where they act as damage-associated molecular patterns (DAMPs) [PMID: 29330312]. These molecules trigger the innate immune system by binding to pattern recognition receptors, such as Toll-like receptors (TLRs) and the cGAS-STING pathway, leading to the production of pro-inflammatory cytokines [PMID: 30612048]. In clinical contexts, eNAs are implicated in the pathogenesis of autoimmune disorders like systemic lupus erythematosus, as well as in sepsis and thrombosis, where they provide a scaffold for clot formation [PMID: 33057343]. Therapeutic interventions primarily involve the use of recombinant nucleases, such as Dornase alfa, to degrade these molecules and alleviate their pathological effects, or the development of cationic polymers to sequester them [PMID: 32853434]. Additionally, eNAs serve as critical biomarkers in liquid biopsies for oncology and prenatal testing, reflecting the genetic landscape of the source tissue [PMID: 28125032].

Other names

Cell-free nucleic acidscfNAExtracellular DNAeDNAExtracellular RNAeRNACirculating nucleic acidsCell-free DNAcfDNACell-free RNAcfRNA

Enzymatic degradation of extracellular DNA or RNA to reduce pro-inflammatory and pro-thrombotic signaling; sequestration or neutralization of nucleic acids using cationic molecules to prevent pattern recognition receptor activation.