Biological safety considerations in the production of health care products from recombinant organisms

Safety considerations in the field of recombinant technology and rDNA production of health care products have been under discussion since the beginning of this technology in 1973 and will certainly go on. However no adverse effects, which could have been attributed to rDNA technology have been observed. On the other hand many life-saving and life-improving drugs have been on the market for many years to the benefit of many patients. New technologies and products thereof often provoke uncertainties about their impact on the environment or society. This article discusses some potential risks in the application of rDNA technology to drugs as well as some benefits for patients, society and environment.     

Advantages of antisense drugs for the treatment of oral diseases

For almost two decades, antisense oligonucleotides (AS-ON) have been used successfully to suppress and regulate gene expression in vitro and in vivo. They are, meanwhile, well established to serve as molecular tools for several biologic applications, from the study of single gene functions up to complex target gene validations. Based on an at least theoretically simple mode of action, the sequence-specific inhibition of mRNA functions after complex formation by Watson-Crick base pairing and presumably enzymatic degradation of the target mRNA, they obviously carry a high therapeutic potential for the treatment of human diseases. In recent years, a remarkable number of clinical trials have been initiated and performed to evaluate the therapeutic usefulness of antisense technology. However, after the successful development of the first antisense-based drug Vitravene (Isis Pharmaceutical Inc., Carlsbad, CA) in 1998, no second product has appeared on the market to date. Here, we describe substantial advantages for the development of antisense-based drugs against less severe oral diseases that represent novel but highly promising application fields of the technology.     

Advances in Lentivirus Purification

Lentiviral vectors (LVs) have been increasingly used as a tool for gene and cell therapies since they can stably integrate the genome in dividing and nondividing cells. LV production and purification processes have evolved substantially over the last decades. However, the increasing demands for higher quantities with more restrictive purity requirements are stimulating the development of novel materials and strategies to supply the market with LV in a cost-effective manner. A detailed review of each downstream process unit operation is performed, limitations, strengths, and potential outcomes being covered. Currently, the majority of large-scale LV manufacturing processes are still based on adherent cell culture, although it is known that the industry is migrating fast to suspension cultures. Regarding the purification strategy, it consists of batch chromatography and membrane technology. Nevertheless, new solutions are being created to improve the current production schemes and expand its clinical use.     

从DNA疫苗到耐受疫苗:全新的适应症和抑炎前景

DNA疫苗技术从1990年代发现到至今,已经创造成功了4个临床兽用疫苗或产品,并仍然有数十个产品正在临床验证的不同阶段。通过不断提高DNA质粒进入体细胞的效率,DNA疫苗将具有更强的免疫应答效率,从而使得DNA疫苗走向更多和更广泛的临床应用。DNA疫苗不仅可以增强机体免疫系统的应答反应,利用其与蛋白质疫苗共免疫的方式也可以产生特异性的免疫耐受反应用于抑制免疫反应。基于DNA疫苗的诱导免疫耐受的疫苗技术开辟了全新的过敏性疾病和自主免疫疾病的干预领域,具有重要的临床潜力和应用前景。     

Current status and perspectives of biopharmaceutical drugs

Since the first approval of recombinant human insulin three decades ago, more than 150 biopharmaceutical drugs have been marketed, and some of them became blockbuster drugs in market size. The patent expiration of the oldest biopharmaceutical drugs resulted in the development of biosimilar drugs. However the short serum half-life of biopharmaceutical drugs incurs a frequent injection to maintain a target clinical outcome in patients. The other major critical concern of biopharmaceutical drugs is immunogenicity producing anti-drug antibodies. These antibodies may reduce clinical efficacy by neutralizing biological activity, and may not only cause a severe allergic reaction but also other serious adverse reactions by blocking endogenous proteins. In order to improve pharmaceutical properties and reduce immunogenicity, the next generation biobetter drugs were achieved by glycoengineering technology, pegylation technology and protein engineering technology. Other biobetter drugs having optimized binding sites were also generated by in vitro display technology. Many of those biobetter drugs have been developed and/or are under development, and come into the clinical field in the near future.     

Economics and politics of the ethanol market

Ethanol is a commodity with potential in both the car fuel sector, thanks to its properties of transportability and efficient combustibility, and in the chemical sector because of its chemical structure and reactivity. However, because the compound is competing with established fuels and chemicals for existing markets rather than creating entirely new ones, there are many practical constraints on its widespread use. If it could be produced cheaply enough in large quantities, and if technology could be developed for its efficient use, then ethanol's potential might be realised. However, potential users of ethanol would be unlikely to develop new processes without a guaranteed supply of cheap ethanol. On the other hand, producers of ethanol have little incentive to improve processes radically without the incentive of a large market. This vicious circle could be broken by political intervention but the intervention must have a valid basis in technology — and not be merely based on political expediency.     

Commercial potential for Haematococcus microalgae as a natural source of astaxanthin

As a result of high production costs, commercial products from microalgae must command high prices. Astaxanthin produced by Haematococcus is a product that has become a commercial reality through novel and advanced technology. Cultivation methods have been developed to produce Haematococcus containing 1.5-3.0% astaxanthin by dry weight, with potential applications as a pigment source in aquaculture, poultry feeds and in the worldwide nutraceutical market.     

Wall Street's assessment of plastic surgery--related technology: a clinical and financial analysis

Many plastic surgeons develop technologies that are manufactured by Wall Street-financed companies. Others participate in the stock market as investors. This study examines the bioengineered skin industry to determine whether it integrates clinical and financial information as Wall Street tenets would predict, and to see whether the financial performance of these companies provides any lessons for practicing plastic surgeons. In efficient markets, the assumptions on which independent financial analysts base their company sales and earnings projections are clinically reasonable, the volatility of a company's stock price does not irrationally differ from that of its industry sector, and the buy/sell recommendations of analysts are roughly congruent. For the companies in this study, these key financial parameters were compared with a benchmark index of 69 biotech companies of similar age and annual revenues (Student's t test). Five bioengineered skin companies were included in the study. Analysts estimated that each company would sell its product to between 24 and 45 percent of its target clinical population. The average stock price volatility was significantly higher for study companies than for those in the benchmark index (p < 0.05). Similarly, buy/sell recommendations of analysts for the study companies were significantly less congruent than those for the benchmark companies (p < 0.05). These results indicate clinically unrealistic projections for market penetration, significantly high price volatility, and significantly high discordance among professional analysts. In all cases, the market is inefficient-an unusual finding on Wall Street. A likely explanation for this market failure is a cycle of poor clinical correlation when assigning sales projections, which in turn leads to price volatility and discordance of buy/sell recommendations. This study's findings have implications for plastic surgeons who develop new technology or who participate in the equities markets as investors. Plastic surgeons who develop new medical devices or technology cannot universally depend on the market to drive clinically reasonable financial performance. Although inflated sales estimates have benefits in the short term, failure to meet projections exacts severe financial penalties. Plastic surgeons who invest in the stock market, because of their unique clinical experience, may sometimes be in the position to evaluate new technologies and companies better than Wall Street experts. Well-timed trades that use this expertise can result in opportunities for profit.     

当前疫苗工业综述

本文系统化的综述了当前一个热门的研发领域-疫苗工业,并详细分析了其背景和潜在的市场,以及中国疫苗工业在发展中可能遇到的机遇和挑战。此外,还对中国疫苗工业存在的某些问题提出了解决方法。只有加强中国生物技术公司在高端疫苗领域的技术水平才能在根本上与国外制药业巨头竞争一席之地,向广大民众提供更好的药物。     

Survey of the year 2006 commercial optical biosensor literature

We identified 1219 articles published in 2006 that described work performed using commercial optical biosensor platforms. It is interesting to witness how the biosensor market is maturing with an increased number of instrument manufacturers offering a wider variety of platforms. However, it is clear from a review of the results presented that the advances in technology are outpacing the skill level of the average biosensor user. While we can track a gradual improvement in the quality of the published work, we clearly have a long way to go before we capitalize on the full potential of biosensor technology. To illustrate what is right with the biosensor literature, we highlight the work of 10 groups who have their eye on the ball. To help out the rest of us who have the lights on but nobody home, we use the literature to address common myths about biosensor technology.     

Analyzing consumers' preferences towards GM food in southern Spain

In Europe, since the 1990s, food safety crises have heightened public concerns about and distrust towards the agro-food sector, making consumers wary of genetically modified (GM) foods. The application of gene technology to agricultural production has become a highly controversial scientific, political and social issue due to the uncertainty about the potential risks and benefits from GM food consumption. In this regard, public views influence consumers' demands and hence determine the future of this technology's development. Biotechnology proponents attribute the current consumer resistance to GM foods to the lack of tangible benefits for the consumers with higher functional properties. Thus, this paper estimates consumers' preferences regarding GM foods by simulating a market for GM functional cornflakes in southern Spain using the conjoint analysis method. Additionally, market segmentation was performed using a cluster analysis and the consumers' profile differences for each segment were identified. The main results indicate that consumers prefer the GM-free food; nonetheless, the market segmentation distinguishes a potential market niche for GM foods and indicates that businesses can develop strategies to target these segments. Therefore, the marketing strategies implemented in southern Spain should be focused on the health functional claims of second generation GM food.     

Commercial potential of RNAi

The commercial potential of RNAi is assessed on the basis of successful translation of technology into applications in three areas: (1) drug discovery and research-currently the biggest segment; (2) potential therapeutic applications; and (3) the role of microRNA in molecular diagnostics. RNAi is an important method for analyzing gene function and identifying new drug targets that use dsRNA to knock down or silence specific genes. Sets of siRNAs focused on a specific gene class (siRNA libraries) have the capacity to greatly increase the pace of pathway analysis and functional genomics. RNAi plays an important role in drug discovery by facilitating target validation. The discovery of the role of microRNA (miRNAs) in various pathological processes opens up possible applications in molecular diagnostics, particularly that of cancer. The advantages of RNAi-based therapeutics over traditional pharmaceuticals include the capability for more specific therapies with small molecule siRNA. Drawbacks include the development of resistance in cancer and viral infections as well as the interferon effect. RNAi is closely related to gene therapy and the vectors developed for gene therapy are also being used for delivery of siRNAs. RNAi, along with other related technologies, will contribute to the development of personalised medicine. Although none of the RNAi-based drugs is in the market yet, some are in clinical trials. By the year 2010 the market for RNAi-based drugs is expected to be worth 3.5 billion dollars and is expected to expand to 10.5 billion dollars by the year 2015.     

Genetic modification; the development of transgenic ornamental plant varieties

Plant transformation technology (hereafter abbreviated to GM, or genetic modification) has been used to develop many varieties of crop plants, but only a few varieties of ornamental plants. This disparity in the rate and extent of commercialisation, which has been noted for more than a decade, is not because there are no useful traits that can be engineered into ornamentals, is not due to market potential and is not due to a lack of research and development activity. The GM ornamental varieties which have been released commercially have been accepted in the marketplace. In this article, progress in the development of transgenic ornamentals is reviewed and traits useful to both consumers and producers are identified. In considering possible factors limiting the release of genetically modified ornamental products it is concluded that the most significant barrier to market is the difficulty of managing, and the high cost of obtaining, regulatory approval.     

Polymer--drug conjugates as nano-sized medicines

Polymer Therapeutics have enormously evolved in the past decades. Several polymeric drugs as well as polymer-protein conjugates have been in the market since the 90s, but although polymer-drug conjugates are already in clinical trials they still need to reach this final goal. There are four main convergent strategies to move this platform technology further. First, exploitation of new molecular targets in cancer therapy and design of polymer-drug conjugates as treatments for other diseases. Second, the development of combination therapy. Third, attempts to improve polymer chemistry, including the use of new well-defined architectures and the optimization of the advanced characterization techniques essential to transform a promising conjugate into a candidate for clinical evaluation. Finally, increased understanding of polymer conjugate features that govern clinical risk-benefit is leading to an appreciation of clinical biomarkers that will open new possibilities for personalized therapy.     

The Resource Basis of Magnetic Refrigeration

Emerging economies such as China and India are currently experiencing a “refrigeration revolution.” Energy spent for domestic cooling is expected to outreach that for heating worldwide over the course of the twenty‐first century. Magnetic refrigeration is an alternative cooling technology that works without gas‐based refrigerants and has the potential to be significantly more energy efficient. We evaluate to what extent the raw materials needed to produce this kind of technology on a mass‐market scale are critical in terms of demand and supply, thus identifying potential supply bottlenecks that might hinder the breakthrough of this promising technology. We assess the criticality of three promising magnetocaloric materials, that is, Gd₅(SiGe)₄, La(FeSi)₁₃, and (MnFe)₂P), as well as of Nd₂Fe₁₄B, as the candidate permanent magnet material to drive the cooling cycle. The Gd‐based alloys are disqualified as a mass‐market refrigerant in terms of resource criticality, whereas La‐ and Mn‐based alloys are much less problematic. Given the current state of technology and projected resource supply, Nd in Nd₂Fe₁₄B magnets would experience a significant bottleneck only at a later innovation stage, that is, when magnetic cooling technology would largely dominate the domestic refrigerator and air‐conditioning market.     

Biofuel alternatives to ethanol: pumping the microbial well

Engineered microorganisms are currently used for the production of food products, pharmaceuticals, ethanol fuel and more. Even so, the enormous potential of this technology has yet to be fully exploited. The need for sustainable sources of transportation fuels has generated a tremendous interest in technologies that enable biofuel production. Decades of work have produced a considerable knowledge-base for the physiology and pathway engineering of microbes, making microbial engineering an ideal strategy for producing biofuel. Although ethanol currently dominates the biofuel market, some of its inherent physical properties make it a less than ideal product. To highlight additional options, we review advances in microbial engineering for the production of other potential fuel molecules, using a variety of biosynthetic pathways.     

基因工程药物研制过程中相关问题探讨

以DNA重组技术为核心的现代生物技术是国际上优先发展的高技术领域之一。以基因工程技术为核心的生物药物已形成一个高新技术产业。利益驱使很多科研单位和企业投入大量资金到基因工程药物的开发中来。在基因工程制药选题立项时应首先考虑产品市场风险、研制过程中的技术风险和国家政策法规的修改所带来的风险;其次,在药学研究、临床前药理药效研究、临床研究、资料申报的具体过程中,要根据产品的具体特性确定好实验方案、工作计划和合作单位,并按药品注册管理办法的要求作好每一阶段的具体工作。就基因工程药物研究过程中的实际问题阐述了一些经验,希望对业内同仁有所帮助。     

Clinical application of urinary proteomics/peptidomics

The technology platforms for proteome analysis have advanced considerably over the last few years. Driven by these advancements in technology, the number of studies on the analysis of the proteome/peptidome, with the aim of defining clinically relevant biomarkers, has substantially risen. Urine has become an increasingly relevant target for clinically oriented proteome analysis; the first clinical trials based on urinary proteomics have been initiated, and studies including several hundred patients have been published. In this article, we summarize the relevant technical aspects in biomarkers discovery and the course from biomarker discovery or ‘potential’ biomarkers to those that have been validated and are clinically important. We discuss experimental design based on the statistics calculated to produce a clinically important end point. We present several examples of proteomic studies that have defined urinary biomarkers for clinical applications, focusing on capillary electrophoresis coupled to mass spectrometry as a technology. Finally, current challenges and considerations for future studies will be discussed.     

Genetic modification in floriculture

Micro-propagation, embryo rescue, mutagenesis via chemical or irradiation means and in vitro inter-specific hybridisation methods have been used by breeders in the floriculture industry for many years. In the past 20 years these enabling technologies have been supplemented by genetic modification methods. Though many genes of potential utility to the floricultural industry have been identified, and much has been learnt of the genetic factors and molecular mechanisms underlying phenotypes of great importance to the industry, there are only flower colour modified varieties of carnation and rose in the marketplace. To a large extent this is due to unique financial barriers to market entry for genetically modified varieties of flower crops, including use of technology fees and costs of regulatory approval.