Wong Mary S, Hawthorne Wayne J, Manolios Nicholas
Department of Rheumatology; University of Sydney; Sydney, NSW Australia.
Self Nonself. 2010 Jul;1(3):165-175. doi: 10.4161/self.1.3.12643. Epub 2010 Jun 9.
Type 1 diabetes (T1D) is a chronic autoimmune disease, whereby auto-reactive cytotoxic T cells target and destroy insulin-secreting β-cells in pancreatic islets leading to insulin deficiency and subsequent hyperglycemia. These individuals require multiple daily insulin injections every day of their life without which they will develop life-threatening diabetic ketoacidosis (DKA) and die. Gene therapy by viral vector and non-viral transduction may be useful techniques to treat T1D as it can be applied from many different angles; such as the suppression of autoreactive T cells to prevent islet destruction (prophylactic) or the replacement of the insulin gene (post-disease). The need for a better method for providing euglycemia arose from insufficient numbers of cadaver islets for transplantation and the immunosuppression required post-transplant. Ectopic expression of insulin or islet modification have been examined, but not perfected. This review examines the various gene transfer methods, gene therapy techniques used to date and promising novel techniques for the maintenance of euglycemia in the treatment of T1D.
1型糖尿病（T1D）是一种慢性自身免疫性疾病，自身反应性细胞毒性T细胞靶向并破坏胰岛中分泌胰岛素的β细胞，导致胰岛素缺乏及随后的高血糖症。这些患者一生中每天都需要多次注射胰岛素，否则会发展为危及生命的糖尿病酮症酸中毒（DKA）并死亡。通过病毒载体和非病毒转导进行基因治疗可能是治疗T1D的有用技术，因为它可以从许多不同角度应用；例如抑制自身反应性T细胞以防止胰岛破坏（预防性）或替换胰岛素基因（疾病发生后）。由于用于移植的尸体胰岛数量不足以及移植后需要免疫抑制，因此需要一种更好的方法来实现血糖正常。已经对胰岛素的异位表达或胰岛修饰进行了研究，但尚未完善。本综述探讨了各种基因转移方法、迄今为止使用的基因治疗技术以及在T1D治疗中维持血糖正常的有前景的新技术。
