Trends in biotechnology

Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants.

Publication Date: 2008 Aug 1 PMID: 18676047
Authors: Spok, A. - Twyman, R. M. - Fischer, R. - Ma, J. K. - Sparrow, P. A.
Journal: Trends Biotechnol

The use of genetically modified (GM) plants to synthesize proteins that are subsequently processed, regulated and sold as pharmaceuticals challenges two very different established regulatory frameworks, one concerning GM plants and the other covering the development of biotechnology-derived drugs. Within these regulatory systems, specific regulations and guidelines for plant-made pharmaceuticals (PMPs) - also referred to as plant-derived pharmaceuticals (PDPs) - are still evolving. The products nearing commercial viability will ultimately help to road test and fine-tune these regulations, and might help to reduce regulatory uncertainties. In this review, we summarize the current state of regulations in different countries, discuss recent changes and highlight the need for further regulatory development in this burgeoning, new industry. We also make the case for the harmonization of international regulations.

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Engineering microbial consortia: a new frontier in synthetic biology.

Publication Date: 2008 Jul 31 PMID: 18675483
Authors: Brenner, K. - You, L. - Arnold, F. H.
Journal: Trends Biotechnol

Microbial consortia are ubiquitous in nature and are implicated in processes of great importance to humans, from environmental remediation and wastewater treatment to assistance in food digestion. Synthetic biologists are honing their ability to program the behavior of individual microbial populations, forcing the microbes to focus on specific applications, such as the production of drugs and fuels. Given that microbial consortia can perform even more complicated tasks and endure more changeable environments than monocultures can, they represent an important new frontier for synthetic biology. Here, we review recent efforts to engineer synthetic microbial consortia, and we suggest future applications.

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Developing therapeutic proteins by engineering ligand-receptor interactions.

Publication Date: 2008 Jul 31 PMID: 18675482
Authors: Jones, D. S. - Silverman, A. P. - Cochran, J. R.
Journal: Trends Biotechnol

Ligand-receptor interactions govern myriad cell signaling pathways that regulate homeostasis and ensure that cells respond properly to stimuli. Growth factors, cytokines and other regulatory elements use these interactions to mediate cell responses, including proliferation, migration, angiogenesis, immune responses and cell death. Proteins that inhibit these processes have potential as therapeutics for cancer and autoimmune disorders, whereas proteins that stimulate these processes offer promise in regenerative medicine. Although much of the focus in this area over the past decade has been on monoclonal antibodies, recently there has been increased interest in the use of non-antibody proteins as therapeutic agents. Here, we review recent advances and accomplishments in the use of rational and combinatorial protein engineering approaches to developing ligands and receptors as agonists and antagonists against clinically important targets.

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Cybrid human embryos - warranting opportunities to augment embryonic stem cell research.

Publication Date: 2008 Jul 31 PMID: 18675481
Authors: Fulka, J. Jr - Fulka, H. - St John, J. - Galli, C. - Lazzari, G. - Lagutina, I. - Fulka, J. - Loi, P.
Journal: Trends Biotechnol

The recent vote in the British Parliament allows scientists in principle to create hybrid embryos by transferring human somatic cell nuclei into animal oocytes. This vote opens a fascinating new area of research with the central aim of generating interspecific lines of embryonic stem cells (ESCs) that could potentially be used to understand development, differentiation, gene expression and genomic compatibility. It will also promote human cell therapies, as well as the pharmaceutical industry's search for new drug targets. If this approach is to be successful, many biological questions need to be answered and, in addition, some moral and ethical aspects must be taken into account.

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Metabolic footprinting in microbiology: methods and applications in functional genomics and biotechnology.

Publication Date: 2008 Jul 31 PMID: 18675480
Authors: Mapelli, V. - Olsson, L. - Nielsen, J.
Journal: Trends Biotechnol

Metabolomics embraces several strategies that aim to quantify cell metabolites in order to increase our understanding of how metabolite levels and interactions influence phenotypes. Metabolic footprinting represents a niche within metabolomics, because it focuses on the analysis of extracellular metabolites. Although metabolic footprinting represents only a fraction of the entire metabolome, it provides important information for functional genomics and strain characterization, and it can also provide scientists with a key understanding of cell communication mechanisms, metabolic engineering and industrial biotechnological processes. Due to the tight and convoluted relationship between intracellular metabolism and metabolic footprinting, metabolic footprinting can provide precious information about the intracellular metabolic status. Hereby, we state that integrative information from metabolic footprinting can assist in further interpretation of metabolic networks.

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Affinity chromatography approaches to overcome the challenges of purifying plasmid DNA.

Publication Date: 2008 Jul 31 PMID: 18675479
Authors: Sousa, F. - Prazeres, D. M. - Queiroz, J. A.
Journal: Trends Biotechnol

The diversity of biomolecules present in plasmid DNA (pDNA)-containing extracts and the structural and chemical similarities between pDNA and impurities are some of the main challenges of improving or establishing novel purification procedures. In view of the unequalled specificity of affinity purification, this technique has recently begun to be applied in downstream processing of plasmids. This paper discusses the progress and importance of affinity chromatography (AC) for the purification of pDNA-based therapeutic products. Several affinity approaches have already been successfully developed for a variety of applications, and we will focus here on highlighting their possible contributions to the pDNA purification challenge. Diverse affinity applications and their advantages and disadvantages are discussed, as well as the most significant results and improvements in the challenging task of purifying plasmids.

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The cult of the amateur in agriculture threatens food security.

Publication Date: 2008 Aug 1 PMID: 18675478
Authors: Trewavas, A.
Journal: Trends Biotechnol

The incorporation of science and technology into agriculture has led to enormous growth in crop yields, providing food security in many countries. From the 1950s onwards there has been increasing interference in agricultural policy by a few scientists who are marginal to agriculture and from a variety of unqualified groups. These groups and individuals have used fear and anxiety and have greatly exaggerated minor problems to persuade an unqualified public of supposed dangers in food and to try and change agricultural policy. Fear and emotion do not lead to good policy, and the cult of the amateur that has developed could have serious repercussions on vital food security and future agriculture in developing countries; it must be soundly rejected.

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Vascularization in tissue engineering.

Publication Date: 2008 Aug PMID: 18585808
Authors: Rouwkema, J. - Rivron, N. C. - van Blitterswijk, C. A.
Journal: Trends Biotechnol

Tissue engineering has been an active field of research for several decades now. However, the amount of clinical applications in the field of tissue engineering is still limited. One of the current limitations of tissue engineering is its inability to provide sufficient blood supply in the initial phase after implantation. Insufficient vascularization can lead to improper cell integration or cell death in tissue-engineered constructs. This review will discuss the advantages and limitations of recent strategies aimed at enhancing the vascularization of tissue-engineered constructs. We will illustrate that combining the efforts of different research lines might be necessary to obtain optimal results in the field.

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Towards practical implementation of bioelectrochemical wastewater treatment.

Publication Date: 2008 Aug PMID: 18585807
Authors: Rozendal, R. A. - Hamelers, H. V. - Rabaey, K. - Keller, J. - Buisman, C. J.
Journal: Trends Biotechnol

Bioelectrochemical systems (BESs), such as microbial fuel cells (MFCs) and microbial electrolysis cells (MECs), are generally regarded as a promising future technology for the production of energy from organic material present in wastewaters. The current densities that can be generated with laboratory BESs now approach levels that come close to the requirements for practical applications. However, full-scale implementation of bioelectrochemical wastewater treatment is not straightforward because certain microbiological, technological and economic challenges need to be resolved that have not previously been encountered in any other wastewater treatment system. Here, we identify these challenges, provide an overview of their implications for the feasibility of bioelectrochemical wastewater treatment and explore the opportunities for future BESs.

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Environmental protection: applying the precautionary principle and proactive regulation to biotechnology.

Publication Date: 2008 Aug PMID: 18584904
Authors: Richmond, R. H.
Journal: Trends Biotechnol

Biotechnology is a broad field encompassing diverse disciplines from agriculture to zoology. Advances in research are occurring at a rapid pace, and applications that have broad implications socially, economically, ecologically and politically are emerging. Along with notable benefits, environmental consequences that affect core quality-of-life issues for present and future generations are materializing. The precautionary principle should be applied to biotechnology research, activities and products, and a strengthened, enforceable and proactive regulatory framework is needed. The environmental impacts of agriculture, aquaculture, genetically modified organisms (GMOs) and even pharmaceuticals are raising public concerns and demonstrate the need for guidance from a variety of social, economic and scientific disciplines to insure the benefits of biotechnology are enjoyed without unacceptable and irreversible environmental costs.

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Application of systems biology for bioprocess development.

Publication Date: 2008 Aug PMID: 18582974
Authors: Park, J. H. - Lee, S. Y. - Kim, T. Y. - Kim, H. U.
Journal: Trends Biotechnol

Random mutagenesis or genetic modification of an organism without consideration of its consequences to the entire system might cause unwanted changes in cellular metabolism. Systems metabolic engineering thus aims to develop strains by performing metabolic engineering within a systems biology framework, in which entire cellular networks are optimized and fermentation and downstream processes are considered at early stages. Thus, regulatory, metabolic and other cellular networks are engineered in an integrated manner. Here, we review the applications of systems biology for the development of strains and bioprocesses by means of several successful examples and, furthermore, discuss future prospects.

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Raising the bar for biofortification: enhanced levels of bioavailable calcium in carrots.

Publication Date: 2008 Aug PMID: 18579243
Authors: Connolly, E. L.
Journal: Trends Biotechnol

Recent efforts to increase the levels of Ca in the edible portions of plants have used a modified calcium/proton antiporter [known as short cation exchanger 1 (sCAX1)] to increase Ca transport into vacuoles. New work has shown that consumption of Ca-fortified carrots results in enhanced Ca absorption. These studies highlight the potential of increasing plant nutrient content through expression of a high-capacity transporter and illustrate the importance of demonstrating that the fortified nutrient is bioavailable.

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Heterologous expression of glycosyl hydrolases in planta: a new departure for biofuels.

Publication Date: 2008 Aug PMID: 18579242
Authors: Taylor, L. E. 2nd - Dai, Z. - Decker, S. R. - Brunecky, R. - Adney, W. S. - Ding, S. Y. - Himmel, M. E.
Journal: Trends Biotechnol

The concept of expressing non-plant glycosyl hydrolase genes in plant tissue is nearly two decades old, yet relatively little work in this field has been reported. However, resurgent interest in technologies aimed at enabling processes that convert biomass to sugars and fuels has turned attention toward this intuitive solution. There are several challenges facing researchers in this field, including the development of better and more specifically targeted delivery systems for hydrolytic genes, the successful folding and post-translational modification of heterologous proteins and the development of cost-effective process strategies utilizing these transformed plants. The integration of these concepts, from the improvement of biomass production and conversion characteristics to the heterologous production of glycosyl hydrolases in a high yielding bioenergy crop, holds considerable promise for improving the lignocellulosic conversion of biomass to ethanol and subsequently to fuels.

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Nanotechnology and aptamers: applications in drug delivery.

Publication Date: 2008 Aug PMID: 18571753
Authors: Levy-Nissenbaum, E. - Radovic-Moreno, A. F. - Wang, A. Z. - Langer, R. - Farokhzad, O. C.
Journal: Trends Biotechnol

Nucleic acid ligands, also known as aptamers, are a class of macromolecules that are being used in several novel nanobiomedical applications. Aptamers are characterized by high affinity and specificity for their target, a versatile selection process, ease of chemical synthesis and a small physical size, which collectively make them attractive molecules for targeting diseases or as therapeutics. These properties will enable aptamers to facilitate innovative new nanotechnologies with applications in medicine. In this review, we will highlight recent developments in using aptamers in nanotechnology solutions for treating and diagnosing disease.

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Multifunctional nanoparticles - properties and prospects for their use in human medicine.

Publication Date: 2008 Aug PMID: 18514941
Authors: Sanvicens, N. - Marco, M. P.
Journal: Trends Biotechnol

A major aim of medicine has long been the early and accurate diagnosis of clinical conditions, providing an efficient treatment without secondary effects. With the emergence of nanotechnology, the achievement of this goal seems closer than ever. To this end, the development of novel materials and devices operating at the nanoscale range, such as nanoparticles, provides new and powerful tools for imaging, diagnosis and therapy. This review focuses on the significant improvements in performance that nanoparticles offer compared with existing technologies relevant to medicine. Specifically, we address the design of multifunctional nanoparticles as an alternative system for drug and gene delivery, which has great potential for therapy in areas, such as cancer and neuropathologies. Moreover, we discuss the controversy generated by the possible toxic health effects of nanoparticles.

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