ADA and severe combined immunodeficiency: While gene addition approaches work well for X-linked SCID (Hacein-Bey-Abina et al., 2002; Pavel-Dinu et al., 2019), ADA-SCID (Aiuti et al., 2009), Wiskott–Aldrich syndrome (WAS) (Braun et al., 2014), RAG1-SCID (Garcia-Perez et al., 2020), and b-globin disease (Dong and Rivella, 2017), for IL7Rα-SCID and for the Hyper IgM syndrome (caused by mutations in the CD40L gene), gene addition with constitutively expressing vectors will cause severe side effects (Kuo et al., 2018).