Over the years, we have made considerable progress to enhance the potency of Rap by targeting it to cancer cells expressing CD22, CD74 and Trop-2, as exemplified by LL2-onconase [36], Rap-hLL1 [37], and Rap(Q)-hRS7 [34], respectively, but have also encountered difficulty in scaled-up production of these prototypes due to relatively low productivity of Rap-hLL1 or Rap(Q)-hRS7 in mammalian cell cultures. The gene discussed is CD22; the disease is cancer.