中国科学院工业生物技术发展路径

随着工程生物学、基因编辑等共性技术的快速发展,工业生物技术领域的颠覆式创新在低碳合成、未来食品、药物开发等工业生物技术领域不断取得颠覆式创新,支撑了生物产业高质量创新发展。工业生物技术正在为变革传统工业制造模式,构建碳中性工业制造路线形成重要科技支撑。本文从战略规划、创新机构、人才建设、基础研究、科技创新、产业推进等方面系统介绍了中国科学院在工业生物技术领域的整体安排、建制化研发与科技进展,并提出了加快工业生物技术发展的建议。     

工业生物技术中DNA合成发展现状及展望

DNA合成是生命科学领域的共性支撑技术和合成生物学的关键使能技术。以合成生物学为基础的工业生物技术持续快速发展,迫切需要更加便捷、经济、安全的DNA来源以满足其日益增长的大规模DNA合成需求。工业化DNA合成在通量、成本、速度等方面的优势日益凸显,有力推动了工业生物技术研发效率的提升和研发成本的下降。但是现有技术在生产过程中还存在着使用大量有机试剂、资源浪费等问题。随着DNA合成规模的持续快速提升,有毒化学品危害、成本负担、环境负担等问题日益突出。本文结合我们的工作实践,对工业生物技术中DNA合成需求、合成策略以及可持续发展面临的问题和解决方案研究进展进行探讨。     

白色生物技术及其应用进展

“白色”生物技术也叫做工业生物技术,是利用某些微生物或酶进行物质转化,生产新产品或改进原有工业处理过程的技术。其产品可生物降解,生产过程能耗低,废弃物少。它是一门涉及生物学、微生物学、分子生物学、化学以及工程学等多学科的研究领域。综述了白色生物技术的产业优势及其涉及的研究领域,并从生物催化、生物材料、生物能源等方面概述了白色生物技术的应用进展。     

Bacteriophages and biotechnology: vaccines, gene therapy and antibacterials

In recent years it has been recognized that bacteriophages have several potential applications in the modern biotechnology industry: they have been proposed as delivery vehicles for protein and DNA vaccines; as gene therapy delivery vehicles; as alternatives to antibiotics; for the detection of pathogenic bacteria; and as tools for screening libraries of proteins, peptides or antibodies. This diversity, and the ease of their manipulation and production, means that they have potential uses in research, therapeutics and manufacturing in both the biotechnology and medical fields. It is hoped that the wide range of scientists, clinicians and biotechnologists currently researching or putting phages to practical use are able to pool their knowledge and expertise and thereby accelerate progress towards further development in this exciting field of biotechnology.     

Managing genetic material to protect intellectual property rights

One of the most important policy instruments for the promotion of further biotechnology development is intellectual property right (IPR) protection. However, one cannot improve upon a biotechnological invention without physical access to the germplasm, making exchanges of genetic material necessary. A formal transfer agreement, which addresses the key issues of ownership, access, use, and equitable benefit-sharing, is a powerful legal instrument for intellectual property. Other restrictions are generally imposed as a result of national and international safety regulations. Forming strategic alliances, such as joint ventures, collaborative research agreements, joint research and development agreements, and manufacturing and distribution alliances to exploit the economic value of genetic material, provides scientists with the mechanisms they need to bring their research material and products to the marketplace. Received 06 November 1997/ Accepted in revised form 24 November 1997     

Current biotechnological developments in Thailand

Thailand is very much aware of the potential and the opportunities in biotechnology and has given the utmost effort into the development of biotechnology. In 1983, the government has set up the National Center for Genetic Engineering and Biotechnology (NCGEB). The center operates through a network of research institutes and laboratories in order to maximize and consolidate the limited resources of the country. The center also plays a key role in formulating policies and plans relating to biotechnology as well as in supporting and coordinating biotechnology research and development. A sum of U.S. $8.6 million has been allocated for an initial 5-year program for R D & E activities. The priority consideration is on utilizing various levels of biotechnology for improvement in agriculture, industrial productivity, health, and environment. To facilitate and strengthen the link between research institutions and the private sector, the high-level Science and Technology Development Board (STDB) was established in 1986, with an initial allocation of U.S. $2.9 million between 1986 to 1992 for biotechnology. At present, there are between 400 to 500 scientists and technologists with M.S. or higher degrees actively working in research and development (R & D) in biotechnology and engineering, mostly in universities and government research laboratories. It is expected that approximately 500 graduates with advanced degrees in biotechnology and related fields will be produced during the 5-year plan (1987 to 1991).     

Indian entrepreneurship in biotechnology comes of age

Biotechnology is one of the fastest growing, knowledge-driven industries in India and is expected to play a key role in shaping India’s rapidly developing economy. Since its inception in 1986 the Department of Biotechnology (DBT) has been guiding to foster growth of Indian biotechnology with a range of initiatives. Indian biotechnology industry registered over 3.0 billion USD revenue generation in 2009–10, which constitutes about 2 % share of the global biotechnology market. More than 300 companies are engaged in different biotechnology sectors in India, majority of which are clustered in western and southern regions. Biopharmaceuticals is the largest biotechnology sector in India with about 62 % market share. Bioservices ranked second due to the upward trend in a range of service oriented research activities. Bioagriculture recorded highest growth in 2009–10 and is dominated by insect resistant transgenic cotton. Bioindustrial, which deals with production of enzymes for different industrial uses, is the smallest biotechnology sector in India with 6 % revenue share.     

国家自然科学基金资助农作物生物技术研究项目现状与展望

近年来,我国农作物生物技术研究和应用取得了很大进展。自然科学基金作为资助自然科学基础性研究的重要渠道之一,资助了大量有关农作物生物技术研究的课题。本文介绍了国家自然科学基金从重大项目、重点项目和面上项目三个层次上资助农作物生物技术研究项目的情况,分析了我国农作物生物技术研究中存在的问题,并展望了国家自然科学基金未来资助农作物生物技术研究的几个重要方面。     

以基地平台为抓手,促进生物技术创新与转化

生物技术领域技术创新与成果转化类基地平台是开展生物技术关键技术研究,推动应用示范、成果转化及产业化的重要载体。通过对近年来我国生物技术领域技术创新与成果转化类基地平台发展现状进行梳理分析,探讨基地平台在促进生物技术创新与转化中的作用,总结优势和不足,为其今后的发展建设提供参考和借鉴。     

中国工业生物技术发展态势分析与展望

现代生物技术逐渐进入大规模产业化阶段,全球生物经济快速发展,工业生物技术作为生物经济的支柱,支撑生物制造、生物能源、生物农业、生物医药、生物环保和生物服务等产业发展。分析和展现了中国近期在工业生物技术领域基础研究、应用研究、技术转化与产业发展方面取得的进展和成就,反映了中国工业生物技术发展的现状与趋势,并提出了未来发展的挑战与机遇。     

Supersynthesis of flavins in microorganisms and its molecular mechanism (review of the literature)

The present review discusses the significance of fundamental research into regulation of flavin biosynthesis for development of the knowledge about mechanisms of overproduction of these compounds and their manufacturing. The pathways of riboflavin, FMN and FAD biosyntheses and their regulation in some bacteria, yeasts and fungi are considered, as well as the recent advances in flavin biotechnology. The modern trends in microbial and enzymatic production of flavins are discussed.     

基于生产工艺管理的生物工程综合性实验设计

生物工程综合性实验课程以企业人才需求为导向,解决实际生产过程中的复杂工程问题为教学目标,利用两步酶转化法制备L-天冬氨酸和L-丙氨酸的工艺路线,结合生物工程专业生产工艺管理的特点,借鉴生产企业现场管理经验,实施四班三运转的实验运行方式。成绩考核加入交接班总结评价与团队协作评价,该课程设置了包含多门专业核心课程原理、方法与实验技术和企业生产管理模式的新型生物工程综合性实验教学内容,并通过教学实践,持续改进,形成完整的实验教学过程与考核机制。生物工程综合性实验课程取得了良好的教学效果,促进了生物工程专业实验教学的发展。     

The commercialization of genome-editing technologies

The emergence of new gene-editing technologies is profoundly transforming human therapeutics, agriculture, and industrial biotechnology. Advances in clustered regularly interspaced short palindromic repeats (CRISPR) have created a fertile environment for mass-scale manufacturing of cost-effective products ranging from basic research to translational medicine. In our analyses, we evaluated the patent landscape of gene-editing technologies and found that in comparison to earlier gene-editing techniques, CRISPR has gained significant traction and this has established dominance. Although most of the gene-editing technologies originated from the industry, CRISPR has been pioneered by academic research institutions. The spinout of CRISPR biotechnology companies from academic institutions demonstrates a shift in entrepreneurship strategies that were previously led by the industry. These academic institutions, and their subsequent companies, are competing to generate comprehensive intellectual property portfolios to rapidly commercialize CRISPR products. Our analysis shows that the emergence of CRISPR has resulted in a fivefold increase in genome-editing bioenterprise investment over the last year. This entrepreneurial movement has spurred a global biotechnology revolution in the realization of novel gene-editing technologies. This global shift in bioenterprise will continue to grow as the demand for personalized medicine, genetically modified crops and environmentally sustainable biofuels increases. However, the monopolization of intellectual property, negative public perception of genetic engineering and ambiguous regulatory policies may limit the growth of these market segments.     

Marine bioprocess engineering: the missing link to commercialization

Success of US biotechnology has been and continues to be dependent on new discoveries and their timely transformation into useful products through bioprocess engineering and a systems approach. Bioprocess engineering is an essential element of ‘generic applied’ or ‘precompetitive’ research. For marine biotechnology, like biopharmaceutical biotechnology, bioprocess engineering represents the key. The many hundreds of tantalizing bioactive compounds discovered and isolated from varied marine organisms over the past decades have led to only minimal commercialization due to the limited availability of the compounds in question. To address international competitiveness and the revitalization of key US industries, the National Science Foundation launched the Engineering Research Centers Program in the mid 1980s. The essential feature of this program is a partnership among academia, industry and the government to develop next-generation technology through cutting-edge research, relevant education and innovative technology transfer. MarBEC (Marine Bioproducts Engineering Center) is a recently established multi-disciplinary engineering-science cooperative effort of the University of Hawaii and the University of California at Berkeley. Additional partners include three federal laboratories—Argonne National Laboratory, the Edgewood Research, Development and Engineering Center and the Eastern Regional Research Center of the US Department of Agriculture—and the Bishop Museum. MarBEC's research program consists of four major thrusts: Production Systems; Marine Bioproducts and Bioresources; Separation and Conversion; and Bioproduct Formulation.     

海洋生物技术催生蓝色生物经济

海洋生物技术是20世纪末国际出现的前沿技术,至今发展势头良好,方兴未艾。在全球经济面临转型换代的关键时刻,蓝色经济渐现端倪。探讨了蓝色生物经济的概念和内涵,评述了海洋生物技术研发前沿与重点应用领域,展望了蓝色生物经济的良好市场前景与可持续发展,提出了加快发展我国蓝色生物经济的策略和建议。     

Bioprinting: an assessment based on manufacturing readiness levels

Over the last decade, bioprinting has emerged as a promising technology in the fields of tissue engineering and regenerative medicine. With recent advances in additive manufacturing, bioprinting is poised to provide patient-specific therapies and new approaches for tissue and organ studies, drug discoveries and even food manufacturing. Manufacturing Readiness Level (MRL) is a method that has been applied to assess manufacturing maturity and to identify risks and gaps in technology-manufacturing transitions. Technology Readiness Level (TRL) is used to evaluate the maturity of a technology. This paper reviews recent advances in bioprinting following the MRL scheme and addresses corresponding MRL levels of engineering challenges and gaps associated with the translation of bioprinting from lab-bench experiments to ultimate full-scale manufacturing of tissues and organs. According to our step-by-step TRL and MRL assessment, after years of rigorous investigation by the biotechnology community, bioprinting is on the cusp of entering the translational phase where laboratory research practices can be scaled up into manufacturing products specifically designed for individual patients.     

农业生物技术领域专利态势分析

专利是技术的有效载体,通过专利态势分析可以在一定程度上有效掌握技术发展脉络及发展趋势。基于专利信息,采用定量数据、定性调研与专家智慧有机结合的方法,从申请趋势、保护市场、领域分布、重要专利权人等多维度分析视角进行农业生物技术领域专利技术态势分析。通过专利态势分析掌握全球农业生物技术专利保护概貌,指出重点方向。在此基础上结合中国农业生物技术领域专利法律状态和专利转让许可状况探讨中国农业生物技术专利保护现状及存在问题,以期支撑中国农业生物技术领域的创新决策。     

Avian embryos and related cell lines: A convenient platform for recombinant proteins and vaccine production

Chick embryos are a significant historical research model in basic and applied sciences. The embryonated eggs have been used for virus inoculation in order to vaccine production for nearly a century. Recently, avian eggs and cell lines derived from embryonated eggs have found wide application in biotechnology. This review will discuss about the unique characteristics of avian eggs in terms of safety, large scale and economical production of recombinant proteins. This system also provides the human‐like glycosylation on target proteins and therefore can be considered as a suitable host for biomanufacturing of humanized monoclonal antibodies and therapeutic proteins. Avian derived cell lines are an alternative for rapid vaccine manufacturing during a pandemic. Based on the latest knowledge in cell and animal transgenesis, the currently available germ cell‐mediated gene transfer system provides a more efficient strategy in gene targeting and creation of transgenic birds that lead to advancements in industrial, biotechnology, and biological research applications. This review covers the recent development of avian fertilized eggs and related cell lines in a variety of human biopharmaceuticals and viral vaccine manufacturing.     

New Developments in Chemical Engineering for the Production of Drug Substances

The pharmaceutical industry is moving towards a profitability gap between increasing costs and decreasing prices. Finally, management has understood that mergers and acquisitions, high throughput screening, and biotechnology alone will not save the companies' earnings. Therefore, classical approaches like the optimization of production technologies for drug substances, that might help to increase profitability, are receiving increasing attention. This paper shows how the combination of innovative components will guide the way to very efficient and cost‐effective production. The first component is the design and manufacturing of production facilities. The second component is a process streamlining of the production process. The key technologies discussed here are process control and miniplant technology. For these technologies a brief outlook on future trends is given.     

Micellar enzymology

Experimental approaches to modelling the enzymatic function of biological membranes are discussed. Emphasis is given to pseudohomogeneous systems such as proteolipid complexes and enzymes in organic solvents; the latter are solubilized with phospholipids or synthetic surfactants. Methods for producing and studying such micellar systems are considered. The key research problems of micellar enzymology are formulated and its relation to enzyme membranology is discussed. Finally, the new potentialities are noted of applied enzymology (biotechnology) offered by application of a colloidal solution of water in organic solvents as a microheterogeneous medium for enzymatic reactions.