Cosecretion of protease inhibitor stabilizes antibodies produced by plant roots
Cosecretion of protease inhibitor stabilizes antibodies produced by plant roots
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DOI：
10.1104/pp.105.074419
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发表时间：
2006-08-01
期刊：
影响因子：
7.4
通讯作者：
Raskin, Ilya
中科院分区：
文献类型：
--
作者：
Komarnytsky, Slavko;Borisjuk, Nikolai;Raskin, Ilya
一个基于植物的系统，用于连续生产单克隆抗体的基础上分泌的免疫球蛋白复合物从植物根到水培介质（根分泌）被改造，以产生高水平的单链和全尺寸的免疫球蛋白。用植物来源的钙网蛋白信号替换单克隆抗体的原始信号肽使抗体产量水平增加2倍。Bowman-Birk丝氨酸蛋白酶抑制剂的共分泌减少了默认分泌途径中免疫球蛋白复合物的降解，并进一步增加了单链IgG抗体的抗体产量，达到每天36.4 μ g/g根干重（1），全尺寸IgG抗体的产量达到每天21.8 μ g/g根干重（4）。这些结果表明，组成型共分泌的蛋白酶抑制剂结合使用的植物信号肽和抗生素标记的无转化系统提供了一种新的策略，以实现高产量的复杂的治疗性蛋白质分泌的植物根。
A plant-based system for continuous production of monoclonal antibodies based on the secretion of immunoglobulin complexes from plant roots into a hydroponic medium (rhizosecretion) was engineered to produce high levels of single-chain and full-size immunoglobulins. Replacing the original signal peptides of monoclonal antibodies with a plant-derived calreticulin signal increased the levels of antibody yield 2-fold. Cosecretion of Bowman-Birk Serprotease inhibitor reduced degradation of the immunoglobulin complexes in the default secretion pathway and further increased antibody production to 36.4 mu g/g root dry weight per day for single-chain IgG(1) and 21.8 mu g/g root dry weight per day for full-size IgG(4) antibodies. These results suggest that constitutive cosecretion of a protease inhibitor combined with the use of the plant signal peptide and the antibiotic marker-free transformation system offers a novel strategy to achieve high yields of complex therapeutic proteins secreted from plant roots.