Key issues to address in future studies along this translational pathway include: (i) examining the ability of HSPC to engraft in vivo in the context of ongoing autoinflammation and active vasculitis; (ii) identifying the optimal target recovery range of ADA2 enzyme activity given that carriers with reduced enzymatic activity are asymptomatic, and therefore lower than normal levels may be therapeutically sufficient; (iii) establishing the optimal conditioning regimen required during gene therapy, aiming for reduced intensity conditioning with limited toxicity. Here, ADA2 is linked to vasculitis.