Three prime repair exonuclease 1 (TREX1)

Three prime repair exonuclease 1 (TREX1) is the **major 3′→5′ DNA exonuclease** in human cells, encoded by the TREX1 gene[1][2]. It removes DNA fragments, particularly during DNA repair, cell division, and apoptosis, thereby preventing accumulation of cytosolic DNA that could otherwise trigger inappropriate immune responses[1][2][3]. TREX1 is essential for **genomic stability** and for suppressing pathological immune activation: **loss-of-function mutations** cause severe disorders such as Aicardi-Goutières syndrome, familial chilblain lupus, and vasculopathy with cerebral leukodystrophy, through mechanisms involving chronic type I interferon signaling[1][2]. TREX1 is also involved in DNA degradation during granzyme A-mediated cell death and is a component of the SET complex. In addition, it can impact viral infections (e.g., HIV) by degrading viral DNA, allowing the virus to evade immune detection[1][3]. There is considerable interest in modulating TREX1 activity for therapeutic benefit, especially in cancer immunotherapy and antiviral strategies, but clinical drugs targeting TREX1 are not yet established[3].

Other names

3' repair exonuclease 13'-5' exonuclease TREX1Deoxyribonuclease III, dnaQ/mutD-likeDNase IIIDRN3

Drugs could inhibit TREX1 to enhance immune stimulation (anti-cancer, antiviral research focus)\nHypothetical: direct enzymatic inhibition, modulation of DNA sensing pathways[3].