Ehsani P, Meunier A, Nato F, Jafari A, Nato A, Lafaye P
Molecular Biology Unit, Institut Pasteur, Avenue Pasteur, 13164 Teheran, Iran.
Plant Mol Biol. 2003 May;52(1):17-29. doi: 10.1023/a:1023902407855.
The two murine single-chain Fv (scFv) genes against human interleukin IL-4 and IL-6 cytokines were cloned in a plant expression vector (pGEJAE1) and mobilized to Agrobacterium tumefaciens. Tobacco leaf discs were co-cultured with Agrobacterium and transferred to selective media for regeneration. The tobacco in vitro plants produced scFvs against human IL-4 and IL-6. Only 8% of transformed plants expressing anti-IL-4 scFv were obtained versus 76% of transformed plants expressing anti-IL-6 scFv. In addition, some plants producing anti-IL-4 and anti-IL-6 scFvs aged more rapidly in in vitro conditions and in greenhouse pots than did control plants. Western blot analysis showed that the transformed Nicotiana tabacum plants contained proteins with an apparent molecular mass on electrophoresis of ca. 32 kDa, corresponding to the predicted size of the scFvs. As entire plant root seemed to accumulate more scFv than did leaves, we decided to continue working with isolated roots. Anti-IL-6 scFvs were detected in cultivated roots and their culture media. Functional anti-IL-6 scFv accounted for 0.16-0.18% of total soluble proteins. The affinity of the anti-IL-6 scFv produced in plants and measured by Biacore was similar to that of scFv produced in Escherichia coli. The high levels of antibody accumulation in isolated roots and secretion into the medium demonstrate the potential for producing recombinant protein in bioreactor systems.
将两个针对人白细胞介素IL-4和IL-6细胞因子的小鼠单链Fv(scFv)基因克隆到植物表达载体(pGEJAE1)中,并导入根癌农杆菌。烟草叶盘与农杆菌共培养,然后转移到选择性培养基上进行再生。烟草离体植株产生了针对人IL-4和IL-6的scFv。表达抗IL-4 scFv的转化植株仅占8%,而表达抗IL-6 scFv的转化植株占76%。此外,一些产生抗IL-4和抗IL-6 scFv的植株在离体条件下和温室花盆中比对照植株衰老得更快。蛋白质印迹分析表明,转化的烟草植株含有电泳时表观分子量约为32 kDa的蛋白质,与scFv的预测大小相符。由于整个植株的根似乎比叶积累了更多的scFv,我们决定继续对离体根进行研究。在培养的根及其培养基中检测到了抗IL-6 scFv。具有功能的抗IL-6 scFv占总可溶性蛋白的0.16 - 0.18%。通过Biacore测定,植物产生的抗IL-6 scFv的亲和力与大肠杆菌中产生的scFv相似。离体根中抗体的高水平积累以及向培养基中的分泌证明了在生物反应器系统中生产重组蛋白的潜力。