Zhang Xing-Hai, Keating Patricia, Wang Xia-Wei, Huang Yi-Hong, Martin James, Hartmann James X, Liu Aimin
Department of Biological Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA,
Mol Biotechnol. 2014 Apr;56(4):369-76. doi: 10.1007/s12033-013-9717-x.
Interleukin-2 (IL-2) is an important T lymphocyte-derived cytokine in the mammalian immune system. Non-native, recombinant IL-2 derived from Escherichia coli is used widely in both medical research and treatment of diseases. Recombinant human IL-2 gene has been expressed in plant nuclear genomes, therefore it can be spread to the environment through pollen. Furthermore, all the plant-produced IL-2 reported thus far had been attached with artificial tags or fusion proteins, which may trigger unintended immunological responses and therefore compromise its full utility as a medicine. To expand the potential of using plant chloroplasts to produce functional native human therapeutic proteins, we inserted an engineered human interleukin-2 (hIL-2)-coding gene, without any tags, into the chloroplast genome of tobacco (Nicotiana tabacum L.). Partially purified hIL-2 protein from the leaves of the transplastomic plants induced in vitro proliferation of IL-2-dependent murine T lymphocytes. Our study demonstrates that plant chloroplasts can serve as a bio-factory for production of an active native human interleukin in a self-contained and therefore environmentally safe manner.
白细胞介素-2（IL-2）是哺乳动物免疫系统中一种重要的T淋巴细胞衍生细胞因子。来源于大肠杆菌的非天然重组IL-2在医学研究和疾病治疗中都有广泛应用。重组人IL-2基因已在植物核基因组中表达，因此它可能通过花粉传播到环境中。此外，迄今为止报道的所有植物产生的IL-2都附着有人工标签或融合蛋白，这可能引发意外的免疫反应，从而影响其作为药物的全部效用。为了扩大利用植物叶绿体生产功能性天然人类治疗蛋白的潜力，我们将一个无任何标签的工程化人类白细胞介素-2（hIL-2）编码基因插入烟草（Nicotiana tabacum L.）的叶绿体基因组中。从转基因植物叶片中部分纯化的hIL-2蛋白可诱导依赖IL-2的小鼠T淋巴细胞在体外增殖。我们的研究表明，植物叶绿体可以作为一个生物工厂，以一种自包含且对环境安全的方式生产活性天然人类白细胞介素。
