These limitations include immune responses and vector persistence, prohormone processing defects, risk of hypoglycemia and lack of physiological regulation, tissue-specific challenges (AAV8 and risk of hepatotoxicity, AAV1 potentially leading to lower insulin secretion in muscle), dose-dependent toxicity and off-target effects, as well as translational barriers in large animals and humans (such as different immunity and AAV serotype tropism). The gene discussed is INS; the disease is Hypoglycemia.