Recombination activating 1 (RAG1) (RAG1)

Recombination activating 1 (RAG1) is a critical enzyme that, along with RAG2, initiates V(D)J recombination, a process essential for the generation of diverse T-cell and B-cell receptors in the adaptive immune system (1, 13). It functions as an endonuclease that introduces double-strand breaks at recombination signal sequences (RSS) flanking antigen receptor gene segments (1, 11). Mutations in the RAG1 gene lead to various primary immunodeficiencies, most notably RAG1-deficient severe combined immunodeficiency (SCID), characterized by a lack of mature T and B cells and life-threatening infections (11, 12). Therapeutic strategies currently focus on autologous hematopoietic stem and progenitor cell (HSPC) gene therapy, where a functional RAG1 gene is introduced via lentiviral vectors (e.g., MB-110) or corrected using CRISPR/Cas9 gene editing (2, 20). These approaches aim to restore immune function while avoiding the complications of allogeneic stem cell transplantation, such as graft-versus-host disease (4, 5).

Other names

V(D)J recombination-activating protein 1RNF74Recombination activating gene 1

Ex vivo gene addition using lentiviral vectors to deliver a functional RAG1 gene; CRISPR/Cas9-mediated gene editing for precise correction of RAG1 mutations in hematopoietic stem and progenitor cells.