Importantly, we also show ex vivo that LV mediated ADA2 gene transfer: (i) restored ADA2 expression and enzymatic activity in CD34+HSPCs derived from a DADA2 patient with severe bone marrow involvement presenting as pure red cell aplasia (PRCA), resulting in the recovery of stem cell proliferative and colony forming unit capacity; (ii) ameliorated macrophage-mediated endothelial activation that drives the vasculitis of DADA2; and (iii) reduced IFN-γ and phosphorylated STAT1 expression in patient-derived macrophages, thus effectively targeting key pathogenic immune pathways of DADA2. The gene discussed is ADA2; the disease is Pure red cell aplasia.