Advancing gene targeting for primary immune deficiencies: Adenine base editing of the human IL2RG locus for correction of SCID-X1

Primary immune deficiencies were some of the first diseases to be effectively treated by gene transfer into hematopoietic stem cells (HSCs). 1 Kohn L.A. Kohn D.B. Gene Therapies for Primary Immune Deficiencies. Front. Immunol. 2021; 12: 648951 Crossref PubMed Scopus (37) Google Scholar Those early studies for X-linked severe combined immunodeficiency (SCID-X1) 2 Hacein-Bey-Abina S. Hauer J. Lim A. Picard C. Wang G.P. Berry C.C. Martinache C. Rieux-Laucat F. Latour S. Belohradsky B.H. et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N. Engl. J. Med. 2010; 363: 355-364 Crossref PubMed Scopus (524) Google Scholar and for adenosine-deaminase-deficient SCID 3 Aiuti A. Cattaneo F. Galimberti S. Benninghoff U. Cassani B. Callegaro L. Scaramuzza S. Andolfi G. Mirolo M. Brigida I. et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N. Engl. J. Med. 2009; 360: 447-458 Crossref PubMed Scopus (864) Google Scholar relied on the use of randomly integrating gamma retroviral vectors. Recent advances in genome editing have made endogenous gene correction a plausible alternative to the use of randomly integrating viral vectors, and an article by L. Zhang et al. in this issue of Molecular Therapy4 Zhang L. Li K. Liu Z. An L. Wei H. Pang S. Cao Z. Huang X. Jin X. Ma X. Restoring T and B cell generation in X-linked severe combined immunodeficiency mice through hematopoietic stem cells adenine base editing. Mol. Ther. 2024; https://doi.org/10.1016/j.ymthe.2024.03.028 Abstract Full Text Full Text PDF Scopus (0) Google Scholar reports a major advance in demonstrating the correction of a human SCID-X1 mutation by adenine base editing in a novel mouse model of the disease.