DNA cross-link repair protein 1C (Artemis) (DCLRE1C)

DNA cross-link repair protein 1C, commonly known as Artemis, is a critical enzyme encoded by the DCLRE1C gene that possesses both 5'-to-3' exonuclease and structure-specific endonuclease activities (UniProt Q96SD1). It plays a pivotal role in the non-homologous end joining (NHEJ) pathway for DNA double-strand break repair and is indispensable for V(D)J recombination, the process required for the maturation of T and B cell receptors (PubMed: 11850616). Mutations in DCLRE1C result in Artemis-deficient Severe Combined Immunodeficiency (ART-SCID), a condition characterized by a profound lack of functional T and B lymphocytes and increased cellular sensitivity to ionizing radiation (NIH: Genetic and Rare Diseases Information Center). Therapeutic strategies targeting this molecule primarily involve gene addition therapy using autologous CD34+ hematopoietic stem and progenitor cells (HSPCs). In this approach, a functional copy of the DCLRE1C gene is delivered into the patient's own stem cells via a lentiviral vector ex vivo, and the modified cells are then re-infused into the patient (NEJM: Cowan et al., 2022). This restoration of Artemis function allows for successful V(D)J recombination and the subsequent development of a functional immune system. Clinical trials have demonstrated that this gene addition approach can achieve T-cell reconstitution and improve clinical outcomes in infants with ART-SCID (ClinicalTrials.gov: NCT03538899).

Other names

ArtemisSNM1CSCIDARS-SCIDDNA cross-link repair 1C protein

Gene addition via lentiviral vector-mediated transduction of autologous CD34+ hematopoietic stem and progenitor cells to restore functional Artemis protein expression.