Cell-free nucleic acid (cfNA) (cfNA)

Cell-free nucleic acids (cfNAs) are extracellular fragments of DNA and RNA found in circulation, primarily released through apoptosis, necrosis, or active secretion [1]. While widely utilized as non-invasive biomarkers for liquid biopsies in oncology and prenatal testing [2], cfNAs also function as damage-associated molecular patterns (DAMPs) that trigger innate immune responses [3]. They activate pattern recognition receptors, such as Toll-like receptors (TLRs) and the cGAS-STING pathway, contributing to the pathogenesis of autoimmune diseases like systemic lupus erythematosus and acute conditions like sepsis [5]. Therapeutic strategies targeting cfNAs involve their enzymatic degradation using agents like Dornase alfa or their neutralization via cationic polymers to prevent inflammatory signaling [4]. Understanding the dynamics of cfNA fragmentation and clearance is critical for both diagnostic precision and the development of novel anti-inflammatory therapies. Consequently, cfNAs represent a unique class of therapeutic targets where the goal is the removal or inactivation of a pathological signaling molecule rather than the modulation of a traditional protein receptor.

Other names

Cell-free DNACell-free RNACirculating nucleic acidExtracellular DNACirculating tumor DNA (ctDNA)cfDNAcfRNA

Enzymatic degradation of extracellular DNA; Sequestration of pro-inflammatory nucleic acids; Inhibition of endosomal Toll-like receptor signaling.