转基因植物生产药用蛋白的研究进展

利用转基因植物作为生物反应器生产具有重要价值的多肽和蛋白质,包括抗体、疫苗、药用蛋白等较之其他生产系统具有很多优越性,已成为当前植物医药基因工程和药物生物技术领域中的研究热点,本文着重就这一领域近年采国内外的研究现状、发展趋势以及目前存在的问题及对策进行综述。     

利用转基因植物生产药用蛋白研究进展

简要评述了国内外利用转基因植物生产药用蛋白的研究现状、发展趋势,以及转基因植物生产药用蛋白的基本方法、应用研究等。尽管目前植物作为药用蛋白的生物反应器受到诸多因素限制,优点与问题并存,但利用转基因植物生产药用蛋白是植物基因工程研究领域的一个新的发展趋势。     

转基因植物生产疫苗和药物的研发进展

与传统的生产方式相比,以转基因植物作为生物反应器生产药用蛋白和疫苗,被认为是成本低廉、安全便捷的技术途径。目前,若干以转基因植物生产的药用蛋白已通过行政审批准予上市,一批转基因植物表达的人用或畜禽用疫苗也进入临床试验。综述了转基因植物生产疫苗和药用蛋白的研发进展与代表性案例,讨论了目前面临的问题与挑战,展望了未来技术发展方向。     

植物生物反应器表达药用蛋白研究新进展

植物生物反应器被称为"分子农田",它具有无限生产重组蛋白的巨大潜力。利用转基因植物表达的重组蛋白具备原有的理化性质和生物活性,从而为人类提供了一种大量生产药用蛋白的安全可靠、经济、方便的新生产体系。目前已广泛运用于工业、农业尤其是生命科学以及医学制造领域。用植物生物反应器产重组疫苗、重组抗体和其他药用蛋白已成为国内外基因工程研究热点之一。然而,转基因植物产物的表达量、下游加工等问题却也成为利用植物生物反应器应用的限制因素。本文就其优势、近三年内国内外转基因植物生产药用蛋白的研究进展、存在问题及对策作一综述。     

转基因植物生产药用蛋白研究进展

转基因植物作为生物反应器能生产医学上有生物活性的药用蛋白,该文对转基因植物生产医药蛋白的种类、途径及优缺点、改进措施进行了阐述。     

叶绿体转基因植物--一种新型生物反应器

叶绿体转基因植物作为生物反应器,具有外源蛋白表达量高和环境安全性好等优点,近年来呈现出诱人的发展前景。本文综述了叶绿体基因工程的优越性,并重点介绍了叶绿体转基因植物作为生物反应器在生产疫苗、药用蛋白及生物可降解塑料等物质方面的最新研究进展。     

叶绿体转基因植物——一种新型生物反应器

叶绿体转基因植物作为生物反应器, 具有外源蛋白表达量高和环境安全性好等优点, 近年来呈现出诱人的发展前景。本文综述了叶绿体基因工程的优越性, 并重点介绍了叶绿体转基因植物作为生物反应器在生产疫苗、药用蛋白及生物可降解塑料等物质方面的最新研究进展。     

乳腺生物反应器的研究现状

乳腺生物反应器是将外源基因在哺乳动物的乳腺中特异表达,以转基因动物的乳腺组织生产药用蛋白。采用乳腺生物反尖器生产药用蛋白质是一种全新的生产模式,它已经成为生物技术领域发展的重要方面。乳腺生物反应器具有能够生产出具有完全生物活性的药用收白,纯化简单,投资少,成本低,对环境没有任何污染等优点,转基因动物生产药用蛋白可以获得巨额经济效益。     

利用转基因植物生产生物药

传统的生物技术常利用哺乳动物细胞、细菌和真菌培养作为转基因系统 ,来生产生物药。鉴于今后对生物药例如治疗贫血的红细胞生成素和治疗糖尿病的胰岛素 ,以及通过基因组研究发现的新的药用蛋白的需求量均将大量增加 ,故有必要利用另一种转基因系统来生产价格既低廉 ,使用又安全的重组生物药。认为适合于上述目的者为高等植物。利用转基因植物来生产重组药用蛋白和肽有很多优点 ,例如 :(1)植物容易转化 ;(2 )使用安全 ,因植物不是人类病原体的宿主 ,故与动物细胞培养比较 ,利用重组植物生产的生物药不论提纯与否 ,都不大有可能污染人类病原…     

转基因植物作为生物反应器生产口蹄疫疫苗的研究进展

利用转基因植物作为生物反应器表达重组蛋白,生产外源蛋白质作为动物疫苗是一个很有吸引力的廉价生产系统,它有可能代替生产成本较高的传统疫苗的发酵生产系统。通过口蹄疫病毒VPI结构蛋白基因在转基因植物中的表达,口蹄疫疫苗已在植物中产生。在植物中生产的抗原能够保持其自身的免疫原性。本文简要综述了近十年来用转基因植物作为生物反应器生产口蹄疫疫苗的研究进展、特点及其应用前景。     

Posttranslational modification of therapeutic proteins in plants

Plants have emerged as an alternative to current systems for the production of therapeutic proteins. The advantages of plants for the low-cost and large-scale production of safe and biologically active mammalian proteins have been documented recently. A major advantage of transgenic plants over production systems that are based on yeast or Escherichia coli is their ability to perform most of the posttranslational modifications (PTMs) that are required for the bioactivity and pharmacokinetics of recombinant therapeutic proteins. Furthermore, recent advances in the control of PTMs in transgenic plants have made it possible for plants to perform, at least to some extent, human-like modifications of recombinant proteins. Hence, plants have become a suitable alternative to animal cell factories for the production of therapeutic proteins.     

Molecular farming of pharmaceutical proteins

Molecular farming is the production of pharmaceutically important and commercially valuable proteins in plants. Its purpose is to provide a safe and inexpensive means for the mass production of recombinant pharmaceutical proteins. Complex mammalian proteins can be produced in transformed plants or transformed plant suspension cells. Plants are suitable for the production of pharmaceutical proteins on a field scale because the expressed proteins are functional and almost indistinguishable from their mammalian counterparts. The breadth of therapeutic proteins produced by plants range from interleukins to recombinant antibodies. Molecular farming in plants has the potential to provide virtually unlimited quantities of recombinant proteins for use as diagnostic and therapeutic tools in health care and the life sciences. Plants produce a large amount of biomass and protein production can be increased using plant suspension cell culture in fermenters, or by the propagation of stably transformed plant lines in the field. Transgenic plants can also produce organs rich in a recombinant protein for its long-term storage. This demonstrates the promise of using transgenic plants as bioreactors for the molecular farming of recombinant therapeutics, including vaccines, diagnostics, such as recombinant antibodies, plasma proteins, cytokines and growth factors. This revised version was published online in August 2006 with corrections to the Cover Date.     

Molecular farming of recombinant antibodies in plants.

'Molecular farming' is the production of recombinant proteins in plants. It is intended to harness the power of agriculture to cultivate and harvest transgenic plants producing recombinant therapeutics. Molecular farming has the potential to provide virtually unlimited quantities of recombinant antibodies for use as diagnostic and therapeutic tools in both health care and the life sciences. Importantly, recombinant antibody expression can be used to modify the inherent properties of plants, for example by using expressed antipathogen antibodies to increase disease resistance. Plant transformation is technically straightforward for model plant species and some cereals, and the functional expression of recombinant proteins can be rapidly analyzed using transient expression systems in intact or virally infected plants. Protein production can then be increased using plant suspension cell production in fermenters, or by the propagation of stably transformed plant lines in the field. Transgenic plants can be exploited to produce organs rich in a recombinant protein for its long-term storage. This demonstrates the promise of using transgenic plants as bioreactors for the 'molecular farming' of recombinant therapeutics, blood substitutes and diagnostics, such as recombinant antibodies.     

重组蛋白在植物体中的表达及其应用

近年来,以植物为生物反应器异源表达和生产具有药用及商业价值的蛋白质发展迅速,某些产品已进入临床试验,且获得了很好的疗效;另一类在植物体中表达的具有重要农艺价值的蛋白质可介导植物抵抗病原体,即植物抗体介导的抗性,是植物抗病原体分子育种的又一途径。介绍了重组蛋白在植物体中表达及其应用的现状。     

重组蛋白在植物体中的表达及其应用

近年来,以植物为生物反应器异源表达和生产具有药用及商业价值的蛋白质发展迅速,某些产品已进入临床试验,且获得了很好的疗效;另一类在植物体中表达的具有重要农艺价值的蛋白质可介导植物抵抗病原体,即植物抗体介导的抗性,是植物抗病原体分子育种的又一途径.介绍了重组蛋白在植物体中表达及其应用的现状.     

Technical enzymes produced in transgenic plants

Technical enzymes are used in many industrial applications. Nowadays technical enzymes are often produced in transgenic host organisms. The use of transgenic plants with respect to high level of expression at low costs as a prerequisite for successful commercial production of technical enzymes is discussed. This review summarises recently published examples for production of technical enzymes in plants. In addition, plastid transformation and viral vectors are discussed as methods which might be useful for obtaining high expression level of recombinant proteins in plants.     

Antibody molecular farming in plants and plant cells

`Molecular Farming' is a novel approach to the production of pharmaceuticals, where valuable recombinant proteins can be produced in transgenic organisms on an agricultural scale. Plants have been traditionally used as a source of medicines, but the use of transgenic plants in molecular farming represents a novel source of molecular medicines that include plasma proteins, enzymes, growth factors, vaccines and recombinant antibodies. Until recently, the wide use of these molecular medicines was limited because of the difficulty in producing these proteins outside animals or animal cell cultures. The application of molecular biology and plant biotechnology in the 1990s showed that many molecular medicines could be synthesised in plants. The goal of this Molecular Farming technology is to produce pharmaceuticals that are safer, easier to produce and less expensive than those produced in animals or microbial cultures. Here, we examine the production of recombinant antibodies by Molecular Farming.     

Nuclear and plastid genetic engineering of plants: Comparison of opportunities and challenges

Plant genetic engineering is one of the key technologies for crop improvement as well as an emerging approach for producing recombinant proteins in plants. Both plant nuclear and plastid genomes can be genetically modified, yet fundamental functional differences between the eukaryotic genome of the plant cell nucleus and the prokaryotic-like genome of the plastid will have an impact on key characteristics of the resulting transgenic organism. So, which genome, nuclear or plastid, to transform for the desired transgenic phenotype? In this review we compare the advantages and drawbacks of engineering plant nuclear and plastid genomes to generate transgenic plants with the traits of interest, and evaluate the pros and cons of their use for different biotechnology and basic research applications, ranging from generation of commercial crops with valuable new phenotypes to ‘bioreactor’ plants for large-scale production of recombinant proteins to research model plants expressing various reporter proteins.     

Recombinant aprotinin produced in transgenic corn seed: extraction and purification studies

Expression in transgenic plants is potentially one of the most economical systems for large-scale production of valuable peptide and protein products. However, the downstream processing of recombinant proteins produced in plants has not been extensively studied. In this work, we studied the extraction and purification of recombinant aprotinin, a protease inhibitor used as a therapeutic compound, produced in transgenic corn seed. Conditions for extraction from transgenic corn meal that maximize aprotinin concentration and its fraction of the total soluble protein in the extract were found: pH 3.0 and 200 mM NaCl. Aprotinin, together with a native corn trypsin inhibitor (CTI), was captured using a tryspin-agarose column. These two inhibitors were separated using an agarose-IDA-Cu2+ column that proved to efficiently absorb the CTI while the recombinant aprotinin was collected in the flowthrough with purity of at least 79%. The high purity of the recombinant aprotinin was verified by SDS-PAGE and N-terminal sequencing. The overall recombinant aprotinin recovery yield and purification factor were 49% and 280, respectively. Because CTI was also purified, the recovery and purification process studied has the advantage of possible CTI co-production. Finally, the work presented here introduces additional information on the recovery and purification of recombinant proteins produced in plants and corroborates with past research on the potential use of plants as biorreactors.