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1.
Recombinant proteins can be produced in a diverse array of plant-based systems, ranging from whole plants growing in the soil to plant suspension cells growing in a fully-defined synthetic medium in a bioreactor. When the recombinant proteins are intended for medical use (plant-derived pharmaceutical proteins, PDPs) they fall under the same regulatory guidelines for manufacturing that cover drugs from all other sources, and when such proteins enter clinical development this includes the requirement for production according to good manufacturing practice (GMP). In principle, the well-characterized GMP regulations that apply to pharmaceutical proteins produced in bacteria and mammalian cells are directly transferrable to plants. In practice, the cell-specific terminology and the requirement for a contained, sterile environment mean that only plant cells in a bioreactor fully meet the original GMP criteria. Significant changes are required to adapt these regulations for proteins produced in whole-plant systems and it is only recently that the first GMP-compliant production processes using plants have been delivered. 相似文献
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Milke Lars Aschenbrenner Jennifer Marienhagen Jan Kallscheuer Nicolai 《Applied microbiology and biotechnology》2018,102(4):1575-1585
Applied Microbiology and Biotechnology - Plants synthesize several thousand different polyphenols of which many have the potential to aid in preventing or treating cancer, cardiovascular, and... 相似文献
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Development of arbuscular mycorrhizal biotechnology and industry: current achievements and bottlenecks 总被引:1,自引:0,他引:1
Miroslav Vosátka Aleš Látr Silvio Gianinazzi Jana Albrechtová 《Symbiosis (Philadelphia, Pa.)》2012,58(1-3):29-37
Advanced scientific knowledge on arbuscular mycorrhizal symbioses recently enhanced potential for implementation of mycorrhizal biotechnology in horticulture and agriculture plant production, landscaping, phytoremediation and other segments of the plant market. The advances consist in significant findings regarding:—new molecular detection tools for tracing inoculated fungi in the field;—the coexistence mechanisms of various fungi in the single root system;—new knowledge on in vitro physiology of the AM fungi grown in root organ cultures;—mechanisms of synergistic interactions with other microbes like PGPR or saprotrophic fungi; discovery of mycorrhiza supportive compounds such as strigolactones. Scientific knowledge has been followed by technological developments like novel formulations for liquid applications or seed coating, mycorrhiza stimulating compounds or new application modes. Still the missing components of biotechnology are appropriate, cheap, highly reproducible and effective methods for inocula purity testing and quality control. Also there is a weak traceability of the origin of the mycorrhizal fungi strains used in commercial inocula. Numerous poor quality products can still be found on the markets claiming effective formation mycorrhiza which have very low capacity to do so. These products usually rely in their effects on plant growth not on support of host plants via formation of effective mycorrhizal symbiosis but on fertilizing compounds added to products. There is growing number of enterprises producing mycorrhiza based inocula recently not only in developed world but increasingly in emerging markets. Also collaboration between private sector and scientific community has an improving trend as the development of private sector can fuel further research activities. Last but not least there is apparent growing pull of the market and increasing tendency of reduction of agrochemical inputs and employment of alternative strategies in planting and plant production. These circumstances support further developments of mycorrhizal inocula production and applications and maturation of the industry. 相似文献
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Microalgae production: technical and economic evaluations 总被引:3,自引:0,他引:3
A review of the various literature data for large-scale algae production costs is described. Costs were updated and recomputed in order to compare the different schemes. Total production costs of a nonprocessed biomass range from US$0.15 to US$4.0 kg(-1), according to various authors. Process performance hypotheses and proposed technologies are analyzed to explain these variations. A cost analysis for a tubular bioreactor system is then presented that shows that, assuming a productivity of 60 tons/ha yr, production costs would range from FF24 to FF29 kg(-1) for such a system. Operating costs as well as fixed charges account for approximately 50% of the cost. Parametric sensitivity of these costs is then analyzed: If productivity would be 30, 45, or 90 tons/ha yr, total cost would be around FF48, FF33 and FF19 kg(-1). Advantages and disadvantages of the proposed tubular technology are finally discussed. 相似文献
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Merethe Bagge Thomas Lübberstedt 《Molecular breeding : new strategies in plant improvement》2008,22(3):319-328
Speed and cost–effective techniques for evaluation of plant materials to provide information before entering the next cycle
of selection are critical for success in plant breeding. Whether or not a ‘new’ technique realizes its potential depends on
technical and economic considerations. Biotechnology-based research tools such as doubled haploid technology and molecular
markers have already demonstrated their value for application in plant breeding. In the area of genomics, implementation of
functional markers (FMs) is currently of particular interest. The pipeline from plant materials to FM data points for any
application includes maceration of plant material, DNA isolation and sample preparation. For each step of this pipeline, a
number of techniques are available, and no single method is ideally suited for all applications. The challenge is to meet
the needs of many different scenarios which are present in a modern breeding programme such as the use of (1) few markers
for genotyping hundreds of samples (e.g., marker assisted backcrossing (MAB)), (2) few markers in thousands of samples (e.g.,
screening for GMO), (3) hundreds to thousands of markers for hundreds to thousands of samples (e.g., genetic characterization
of breeding materials (fingerprinting)). This paper compares different techniques for each of the steps from plant material
to FM data point, with the main emphasis on SNP detection platforms, assuming that multiple FMs will become available in the
near future. We focus on technical and economic aspects and discuss which techniques are most suitable for each of the scenarios
using wheat as a model. 相似文献
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The recent technological advances in next generation sequencing have brought the field closer to the goal of reconstructing all genomes within a community by presenting high throughput sequencing at much lower costs. While these next-generation sequencing technologies have allowed a massive increase in available raw sequence data, there are a number of new informatics challenges and difficulties that must be addressed to improve the current state, and fulfill the promise of, metagenomics. 相似文献
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Dingermann T 《Biotechnology journal》2008,3(1):90-97
Since the approval of insulin in 1982, more than 120 recombinant drug substances have been approved and become available as extremely valuable therapeutic options. Exact copying of the most common human form is no longer a value per se, as challenges, primarily related to the pharmacokinetics of artificial recombinant drugs, can be overcome by diverging from the original. However, relatively minor changes in manufacturing or packaging may impact safety of therapeutic proteins. A major achievement is the development of recombinant proteins capable of entering a cell. Such drugs open up completely new opportunities by targeting intracellular mechanisms or by substituting intracellularly operating enzymes. Concerns that protein variants would cause an intolerable immune response turned out to be exaggerated. Although most recombinant drugs provoke some immune response, they are still well tolerated. This knowledge might result in a change in attitude towards antibody formation, i.e., neutralizing antibody activity (in vitro) may be overcome by dosing consistently on the basis of antibody titers and not only on body weight. As with other drugs, efficacy and safety of therapeutic proteins have to be demonstrated in clinical studies, and superiority over available products has to be proven instead of just claimed. 相似文献
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Vola R. Lombardi A. Tarditi L. Zaccolo M. Neri D. Björck L. Mariani M. 《Cell biochemistry and biophysics》1994,24(1-3):27-36
Several bacterial cell wall proteins, like proteins A and G, with valuable affinity for immunoglobulins have been discovered
and are currently employed in immunological techniques. In 1988, protein L, a bacterial cell wall protein with Ig-binding
capacity, was isolated from the anaerobic bacterial speciesPeptostreptococcus magnus. Binding data with immunoglobulin fragments suggested that protein L could selectively bind the variable region of human
kappa light chains. More recently a recombinant LG fusion protein was expressed inE. coli containing four repeated Ig-binding domains of protein L (fragment B1–4) and two IgG Fc-binding protein G domains (fragment
CDC). Recombinant L and LG proteins were tested in the purification of murine monoclonal IgG and their fragments. After affinity-constant
evaluation in different buffer systems, high-pressure affinity-chromatography columns were prepared by coupling the proteins
to Affi-prep 10 resin and tested with eight different murine monoclonal antibodies and their fragments of various isotypes.
Affinity-chromatography experiments confirming radioimmunoassay results showed 75% fragment-binding capacity of protein L
and 100% of protein LG. These results evidenced protein LG as the most powerful Ig-binding tool so far described. Therefore,
application of these proteins may be suggested in the purification of murine immunoglobulins and their fragments, including
the engineered ones. 相似文献
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Both chicken egg-white avidin and its bacterial relative streptavidin are well known for their extraordinary high affinity with biotin (Kd approximately 10(-15) M). They are widely used as tools in a number of affinity-based separations, in diagnostic assays and in a variety of other applications. These methods have collectively become known as (strept)avidin-biotin technology. Biotin can easily and effectively be attached to different molecules, termed binders and probes, without destroying their biological activity. The exceptional stability of the avidin-biotin complex and the wide range of commercially available reagents explain the popularity of this system. In order by genetic engineering to modify the unwanted properties of avidin and to further expand the existing avidin-biotin technology, production systems for recombinant avidin and avidin-fusion proteins have been established. This review article presents an overview of the current status of these systems. Future trends in the production and applications of recombinant avidin and avidin-fusion proteins are also discussed. 相似文献
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Lactoferrin, the main iron-binding protein of milk, has biological activities that are essential for the newborn and are beneficial for adults. Given this beneficial effect, there is broad interest in exogenous sources of lactoferrin in human nutrition. Consequently, several transgenic approaches to produce lactoferrin have been achieved. However, the activity of heterologous lactoferrin cannot be assumed to identically mimic that of the homologous protein. Human lactoferrin obtained from yeast, transgenic cows, and rice has met the criteria of structural similarity, high yield, and ease of protein isolation. Human lactoferrin from Aspergillus awamori has been mainly directed to therapeutic uses with advanced phases of clinical trials currently in progress. In contrast, human lactoferrin produced in transgenic cows and rice brings the clear advantage of origins compatible with use in foods, although the approval for these applications is still in process. 相似文献
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Smads transduce intracellular signals initiated by members of the transforming growth factor beta (TGF beta) family, including activins, TGF betas, and bone morphogenetic proteins. Recently, various models concerning the mechanism of Smad action have been proposed; however, these models are basically qualitative. Quantitative verification of the validity of the models requires significant amounts of purified Smad proteins, but purification of full-length Smad protein has not been straightforward even using recombinant protein expression systems. Here, we report purification of Smad proteins expressed in E. coli as glutathione S-transferase-fused proteins. By glutathione-Sepharose affinity purification, ATP treatment, DEAE-Sepharose and hydroxylapatite columns, expressed Smads were purified to near homogeneity as judged by SDS-PAGE; protein recovery was ca. 1 mg/l culture for Smad2 and 100 microg/l culture for Smad4. The purified Smad proteins had three known in vitro activities: Smad2 phosphorylation by TGF beta receptor complexes immunoprecipitated from COS7 cells, Smad4 binding to Smad-binding DNA element, and Smad2 interaction with calmodulin. The data suggest that purified proteins could be useful for biochemical analyses to evaluate the current models quantitatively. 相似文献
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Recombinant immunotherapeutics are important biologics for the treatment and prevention of various diseases. Immunotherapy
can be divided into two categories, passive and active. For passive immunotherapy, the successes of antibody and cytokine
therapeutics represent a promising future and opportunities for improvements. Efforts, such as cell engineering, antibody
engineering, human-like glycosylation in yeast, and Fab fragment development, have led the way to improve antibody efficacy
while decreasing its high manufacturing costs. Both new cytokines and currently used cytokines have demonstrated therapeutic
effects for different indications. As for active immunotherapy, recently approved HPV vaccines have encouraged the development
of preventative vaccines for other infectious diseases. Immunogenic antigens of pathogenic bacteria can now be identified
by genomic means (reverse vaccinology). Due to the recent outbreaks of pandemic H1N1 influenza virus, recombinant influenza
vaccines using virus-like particles and other antigens have also been engineered in several different recombinant systems.
However, limitations are found in existing immunotherapeutics for cancer treatment, and recent development of therapeutic
cancer vaccines such as MAGE-A3 and NY-ESO-1 may provide alternative therapeutic strategy. 相似文献
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Plantibodies: applications, advantages and bottlenecks 总被引:19,自引:0,他引:19
Various strategies have been developed to exploit plants as bioreactors for the production of pharmaceutical antibodies, to engineer antibody-mediated pathogen resistance or to alter the plant phenotype by immunomodulation. Recent research developments focus on the fine-tuning of expression systems and the detailed characterisation of recombinant products, including the implications of plant-specific glycosylation. Meanwhile, the first of these plant-derived antibody products has successfully completed early phase clinical trials. 相似文献
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D T Liu 《Trends in biotechnology》1992,10(10):364-369
Most protein molecules undergo some degree of spontaneous deamidation in vivo. This process may also occur during the production, isolation, purification, formulation and storage of pharmaceutical proteins. Deamidation is a potential source of microheterogeneity for pharmaceutical proteins, and this is an important issue that needs to be addressed, not only by the manufacturers but also by the national control agencies. This article provides an overview of the scientific and regulatory issues pertinent to deamidation of pharmaceutical proteins. 相似文献
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Sowing the seeds of success: pharmaceutical proteins from plants 总被引:15,自引:0,他引:15
Among the many plant-based production systems that have been developed for pharmaceutical proteins, seeds have the useful advantage of accumulating proteins in a relatively small volume and in a stable environment in which they are protected from degradation. Several seed crops, including cereals, grain legumes and oilseeds, have been explored as production platforms, and the first commercial products -- all technical proteins and enzymes -- have already reached the market. Recent studies have explored the use of seeds for the production of pharmaceutical proteins, particularly replacement human proteins, recombinant antibodies and (oral) vaccines. 相似文献