Arakawa T, Yu J, Chong D K, Hough J, Engen P C, Langridge W H
Center for Molecular Biology and Gene Therapy, Department of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, CA 92350, USA.
Nat Biotechnol. 1998 Oct;16(10):934-8. doi: 10.1038/nbt1098-934.
Oral administration of disease-specific autoantigens can prevent or delay the onset of autoimmune disease symptoms. We have generated transgenic potato plants that synthesize human insulin, a major insulin-dependent diabetes mellitus autoantigen, at levels up to 0.05% of total soluble protein. To direct delivery of plant-synthesized insulin to the gut-associated lymphoid tissues, insulin was linked to the C-terminus of the cholera toxin B subunit (CTB). Transgenic potato tubers produced 0.1% of total soluble protein as the pentameric CTB-insulin fusion, which retained GM1-ganglioside binding affinity and native antigenicity of both CTB and insulin. Nonobese diabetic mice fed transformed potato tuber tissues containing microgram amounts of the CTB-insulin fusion protein showed a substantial reduction in pancreatic islet inflammation (insulitis), and a delay in the progression of clinical diabetes. Feeding transgenic potato tissues producing insulin or CTB protein alone did not provide a significant reduction in insulitis or diabetic symptoms. The experimental results indicate that food plants are feasible production and delivery systems for immunotolerization against this T cell-mediated autoimmune disease.
口服疾病特异性自身抗原可预防或延缓自身免疫性疾病症状的出现。我们已培育出转基因马铃薯植株，其可合成人胰岛素（一种主要的胰岛素依赖型糖尿病自身抗原），含量高达总可溶性蛋白的0.05%。为了将植物合成的胰岛素直接递送至肠道相关淋巴组织，胰岛素与霍乱毒素B亚基（CTB）的C末端相连。转基因马铃薯块茎产生了0.1%的总可溶性蛋白作为五聚体CTB-胰岛素融合蛋白，其保留了GM1-神经节苷脂结合亲和力以及CTB和胰岛素的天然抗原性。给非肥胖糖尿病小鼠喂食含有微克量CTB-胰岛素融合蛋白的转基因马铃薯块茎组织，可使胰岛炎症（胰岛炎）显著减轻，并延缓临床糖尿病的进展。单独喂食产生胰岛素或CTB蛋白的转基因马铃薯组织，并未使胰岛炎或糖尿病症状显著减轻。实验结果表明，食用植物是针对这种T细胞介导的自身免疫性疾病进行免疫耐受诱导的可行生产和递送系统。
