Budzianowski Jaromir
Katedra i Zakład Botaniki Farmaceutycznej i Biotechnologii Roślin, Uniwersytet Medyczny im. Karola Marcinkowskiego, Poznań.
Przegl Lek. 2009;66(10):894-7.
Over one hundred of biopharmaceuticals present on the pharmaceutical market--among them mainly therapeutically peptides and proteins such as hormones, enzymes, interferons, blood factors, monoclonal antibodies, vaccines, growth factors and fusion proteins, are manufactured through recombinant DNA technology in cultures of transgenic bacterial (Escherichia coli), yeast (Saccharomyces cerevisiae) and mammalian cells (CHO, BHK) and rarely insect cells or insects (Bombyx mori). High costs of their manufacturing with simultaneous increased demand for existing and new biopharmaceuticals prompt for the search of cheaper methods of production by using transgenic domestic animals and, in particular, in transgenic crop plants. Among many plant species investigated for ability to produce biopharmaceuticals, such like cereals, legumes, oil plants, vegetables and fruit plants, aquatic plants and mosses, the outstanding features posses two tobacco species--Nicotiana tabacum and Nicotiana benthamiana. Foreign proteins can be expressed in those plants not only in nuclear genome, but also easily in chloroplast genome, through transient transformation and propagation of transgenic plant virus--e.g. tobacco mosaic virus (TMV). Tobacco was shown to be useful to produce various therapeutical proteins, even such complex ones as antibodies including secretory immunoglobulin A (sIgA), with partial humanization of N-glycans. Especially important is possibility of rapid preparation, even within a week, vaccines and monoclonal antibodies for clinical tests or personalized anticancer therapy through transient transformation or infection with transgenic virus. Tobacco with foreign gene may be employed for manufacture in two ways--either in field or green-house cultivation or in the form of in vitro suspension cell culture. Among many biopharmaceuticals expressed in tobacco, several vaccines and antibodies are in advanced stages of development, in clinical evaluations and probably close to application in medicine.
目前医药市场上有一百多种生物制药产品,其中主要是治疗性肽和蛋白质,如激素、酶、干扰素、血液因子、单克隆抗体、疫苗、生长因子和融合蛋白,它们是通过重组DNA技术在转基因细菌(大肠杆菌)、酵母(酿酒酵母)和哺乳动物细胞(CHO、BHK)的培养物中生产的,很少通过昆虫细胞或昆虫(家蚕)生产。其生产成本高昂,同时对现有和新型生物制药的需求不断增加,促使人们寻求利用转基因家畜,特别是转基因作物来寻找更廉价的生产方法。在众多被研究具有生产生物制药能力的植物物种中,如谷物、豆类、油料植物、蔬菜和水果植物、水生植物和苔藓,两种烟草——烟草和本氏烟草具有突出特点。外源蛋白不仅可以在这些植物的核基因组中表达,还可以通过转基因植物病毒(如烟草花叶病毒,TMV)的瞬时转化和繁殖,轻松地在叶绿体基因组中表达。烟草已被证明可用于生产各种治疗性蛋白质,甚至是诸如包括分泌型免疫球蛋白A(sIgA)在内的抗体等复杂蛋白质,其N-聚糖部分人源化。特别重要的是,通过瞬时转化或感染转基因病毒,甚至可以在一周内快速制备用于临床试验或个性化抗癌治疗的疫苗和单克隆抗体。带有外源基因的烟草可通过两种方式用于生产——在田间或温室种植,或以体外悬浮细胞培养的形式。在烟草中表达的众多生物制药产品中,有几种疫苗和抗体正处于开发的后期阶段,正在进行临床评估,可能即将应用于医学领域。