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[Gene technology in production of modern drugs].

In the last years gene technology has influenced dramatically medical and biological disciplines. With the help of molecular biology it is possible to produce a variety of proteins in alternative ways. Further, substances can be produced which exist in nature only in trace amounts, and therefore can not be produced with conventional methods. However, there is no other scientific discipline which is discussed so controversially in public like genetic engineering. The "new" biology comprises a multitude of disciplines which are difficult to understand for non experts. Unfortunately, gene technology has become the new symbol for "uncontrolled" technology development. In this review article the basic concepts of genetic engineering will be explained. Further, the production of some recombinant drugs, which are already used in practice, will be demonstrated. Finally, some safety aspects concerning about risk assessment are discussed.

Animals↗

[Can gene technology in agriculture prevent hunger in the world?].

The world population grows rapidly: the number of mouths to feed increases. Is an agriculture without gene technology able to produce sufficiently in order to prevent hunger? Research indicates that hunger is not the result of short comings in agricultural outputs. It is however the result of poverty. This problem will not be solved by gene technology based agricultural production. This article explains the basic principles of mainstream and organic farming. Literature shows that the production potentials of both kinds of farming are, by far most, not yet exhausted. Gene technology is therefore unnecessary.

Agriculture↗

Gene technology and social acceptance.

About 10% of the human genome has now been mapped and for more than 1000 diseases closely linked DNA polymorphisms or the responsible genes have been identified. These developments have extended the scope of (prenatal) diagnosis and carrier detection which already was possible by biochemical analysis of protein defects in some 400 Mendelian disorders. Together with the study of chromosomal aberrations these activities form the basis for genetic counselling and carrier screening programmes. A brief overview of the activities in clinical genetics will be presented and their importance for the prevention of congenital disorders and for informed decisions of couples at risk will be emphasized. Reproductive decisions are, however very closely related to culture, religion, education and the socioeconomic status of individuals and populations. Up to now genetic services have mainly been developed in wealthy postindustrial countries with a low infant mortality. But even among these countries there are major differences in the implementation of gene technology as will be shown by comparisons of the United States, Europe and Japan. In the developing countries where about 95% of the world's future children will be born there are major hindrances in the development of clinical genetics such as poverty, illiteracy of women, low contraceptive use and a high infant mortality. There are, however, examples of developing countries that give high priority to the application of gene technology such as Cuba and China. While the developing countries are struggling to improve their basic health care, research on gene technology in the western countries proceeds fast. The early identification of a particular gene constitution will show whether a young adult is at higher risk of important diseases such as various forms of cancer, cardiovascular disease, diabetes or psychiatric disorders. The therapeutical, preventive, psychological and some ethical aspects of this new era of predictive medicine will be discussed.

Clinical Medicine↗

Brain drug targeting and gene technologies.

Brain drug targeting technology is based on the application of four gene technologies that enable the delivery of drugs or genes across the blood-brain barrier (BBB) in vivo. I) Genetic engineering is used to produce humanized monoclonal antibodies that target endogenous BBB transporters and act as vectors for delivery of drugs or genes to the human brain. The conjugate of a neurotherapeutic and a BBB transport vector is called a chimeric peptide. Epidermal growth factor chimeric peptides have been used for neuroimaging of brain cancer. Brain-derived neutrophic factor chimeric peptides have marked neuroprotective effects in brain stroke models. II) Imaging gene expression in the brain in vivo is possible with sequence-specific antisense radiopharmaceuticals, which are conjugated to BBB drug targeting vectors. III) Brain gene targeting technology enables widespread expression of an exogenous gene throughout the central nervous system following an intravenous injection of a non-viral therapeutic gene. IV) A BBB genomics program enables the future discovery of novel transport systems expressed at the BBB. These transporters may be carrier-mediated transport systems, active efflux transporters, or receptor-mediated transcytosis systems. The future discovery of novel BBB transport systems and the application of brain drug targeting technology will enable the delivery to the brain of virtually any neurotherapeutic, including small molecules, large molecules and gene medicines.

Animals↗

[The role of chemical synthesis of DNA in gene technology (author's transl)].

A review of applications of chemically synthesized oligodeoxynucleotides to gene technology is given. At first the reader is briefly introduced to the methods of oligodeoxynucleotide synthesis. With selected examples the utilization of synthetic oligodeoxynucleotides is discussed in some detail for sequencing DNA and RNA, for the incorporation of base analogs and sequence specific mutations into nucleic acids of natural origin, for the isolation of specific nucleic acid sequences from biological sources, for the specific inhibition of virus reproduction, as linker molecules for gene cloning experiments and for the total synthesis of signal structures (regulatory sequences) and structural genes. The importance of synthetic oligodeoxynucleotides for molecular biology and gene technology especially is emphasized.

Base Sequence↗

A genomic approach to gene fusion technology.

Gene expression profiling provides powerful analyses of transcriptional responses to cellular perturbation. In contrast to DNA array-based methods, reporter gene technology has been underused for this application. Here we describe a genomewide, genome-registered collection of Escherichia coli bioluminescent reporter gene fusions. DNA sequences from plasmid-borne, random fusions of E. coli chromosomal DNA to a Photorhabdus luminescens luxCDABE reporter allowed precise mapping of each fusion. The utility of this collection covering about 30% of the transcriptional units was tested by analyzing individual fusions representative of heat shock, SOS, OxyR, SoxRS, and cya/crp stress-responsive regulons. Each fusion strain responded as anticipated to environmental conditions known to activate the corresponding regulatory circuit. Thus, the collection mirrors E. coli's transcriptional wiring diagram. This genomewide collection of gene fusions provides an independent test of results from other gene expression analyses. Accordingly, a DNA microarray-based analysis of mitomycin C-treated E. coli indicated elevated expression of expected and unanticipated genes. Selected luxCDABE fusions corresponding to these up-regulated genes were used to confirm or contradict the DNA microarray results. The power of partnering gene fusion and DNA microarray technology to discover promoters and define operons was demonstrated when data from both suggested that a cluster of 20 genes encoding production of type I extracellular polysaccharide in E. coli form a single operon.

Artificial Gene Fusion↗

Gene technology in medical diagnostics and criminal procedure and liability for malpractice in Germany.

The increasing employment of gene technological procedures in medical diagnostics and criminal procedure has forced both the medical and the legal professions to focus their attention on the complex question of liability of physicians, lab technicians, and other personnel involved in applying these measures. This article gives an outline, by citing practical cases, of the major aspects of liability for malpractice that are relevant under German law. Bearing in mind that this article will be read predominantly by members of the Anglo-American common-law legal system, the legal aspects - even though they are German legal aspects - are viewed in the light of the common law. The article examines three major issues: (a) liability for diagnoses employing gene technological procedures: (b) liability for wrong testimony based on 'genetic finger-printing': and (c) the donor's rights concerning his or her DNA-probe.

DNA Fingerprinting↗

[Clinical application of gene technology for diagnosis and treatment of leukemia].

Recently, clinical application of gene technology in oncology and hematology has been markedly advanced. Pathogenesis of leukemic transformation has been thought that it was resulted from cumulation of activation or mutation in oncogenes or onco-suppressor genes. As a matter of fact, many specific chromosomal abnormalities in leukemias have been thought to be due to production of chimeric fusion gene by translocation and activation in some kinds of oncogenes under specific regulatory genes after translocation. In addition to those, inactivation of onco-suppressor genes, such as RB gene or p53 gene, may be also related to leukemogenesis in some leukemias. Laboratory examinations using molecular technology are being necessary for clinical diagnosis and treatment in many hematological disorders. The examinations detecting rearrangement of major BCR or minor BCR in Ph1 positive leukemias, TCR in T cell malignancy, immunoglobulin in B cell malignancy, PML-RAR alpha fusion gene in APL have become routine for diagnosis of some leukemias. Moreover, these examinations are useful for judgement of treatment effects and evaluation of minimal residual diseases. In this paper, we also discuss the usefulness and importance of these technology especially in stem cell transplantation and cytokine therapy, and the future possibility in this technology for gene therapy.

Cytokines↗

Gene technology: chances for diagnosis and therapy.

In the case of a single gene defect, a number of appropriate gene probes are available for prenatal diagnosis. In some cases, knowledge of the genetic disorders enables early onset of therapy or the option for abortion. However, gene technology which enables the diagnosis should not be viewed from an ethical point of view but rather the action taken when diagnostic results are available. Gene therapy for a single gene defect still is at the early stage of development. Only a few patients have been treated in various indications. Difficult to overcome are the low frequency and unspecific integration of inserted DNA into the chromosome, lack of sufficient transcription control, and short half-life of the integrated gene. From an ethical perspective gene therapy complies with the therapeutic concept of medicine. Antisense oligonucleotides are under clinical development for blockage of the synthesis of oncogenes and viral proteins. Stability of oligonucleotides as well as selectivity for specific cells will have to be overcome for broader application. Its therapeutic application is in accordance with the ethical principles of medicine. Substitution therapies with recombinant DNA derived human proteins are in therapeutic application to replace their counterparts from native source in a safer way or for human pharmacologically active proteins which cannot be isolated from their natural source. For recombinant DNA derived proteins where the mode of action is known, short development time frames can be expected allowing for an early return on investment. The expected market potential for recombinant DNA derived pharmaceuticals in 1995 will reach 4,400 million DM. Due to their specificity, monoclonal antibodies are used for tumor imaging when labeled by 99mtechnetium or for tumor therapy when labeled by rhenium or yttrium. Both concepts are under clinical evaluation. Vaccines derived from recombinant DNA technology offer the chance of producing safer vaccines consisting of the antigen determinant only. In general, recombinant DNA technology and biotechnology offer the opportunity of providing new diagnostic and therapeutic principles of high ethical value. The biotechnical manufacturing processes used for this purpose are friendly to the environment by using raw material from renewable sources, low energy consumption, and producing biodegradable products only. In almost all cases, host cells used for manufacturing belong to the safety category 1, in which no danger is expected for the operator, the public, and the environment.(ABSTRACT TRUNCATED AT 400 WORDS)

Biopharmaceutics↗

Gene technology and tissue engineering.

The interest in gene therapy to treat human diseases has increased with the advances in recombinant DNA technology and the improved physical, chemical and biological methods of delivering genes to mammalian cells. Areas of therapeutic interest for gene therapy relevant for tissue engineering are, for example, in the treatment of wounds, skin diseases, nerve, bone, and muscle diseases. The transfer of a gene into a cell can lead to the addition or modification of a function and may be an attractive alternative to the pharmacological use of proteins. The complementation of defective functions could also be an effective treatment for inherited skin diseases with a gene defect. The two major challenges facing gene technology in tissue engineering are the problem of identifying appropriate genes that are effective in tissue repair, and the reliable expression of the therapeutic gene at clinically beneficial levels. This review discusses principles and methods of delivering genes encoding growth factors into cells, together with their respective advantages and disadvantages.

Journal Article↗

[Study on expression of genes in Tamarix androssowii under NaHCO3 stress using gene chip technology].

Gene chip technology was employed to study gene expression in Tamarix androssowii under NaHCO3 stress. cDNAs from T. androssowii treated with NaHCO3 solution and that from control group were labeled with fluorescent dye CyS and Cy3 respectively. The two fluorescent cDNA probes were mixed and hybridized to gene chips containing T. androssowii genes, and the chips were scanned using biochip scanning system. Differential expression of genes was analyzed through calculation of the ratio of Cy5 to Cy3 signal intensities. Total of 89 genes differentially expressed were identified, among them, 27 showed down regulated expression and 62 showed up regulated expression. Blastx analysis showed that the function of the differentially expressed genes could be grouped into some categorizations such as photosynthesis, reactive oxygen species eliminated, regulation of osmotic potential, regulation of gene expression and signal transduction, metabolism, development, ribosomal protein, protein breakdown and recycling, transporter, water channel proteins and so on. Based on this research, some function-unknown or novel unreported genes that respond to salt stress were also identified, and these genes may have important functions in salt resistance of T. androssowii. Some important pathways of salt resistance in T. androssowii are revealed, and the gene expression profiling of T. androssowii under salt stress and without stress is obtained in this study.

DNA, Complementary↗

[Gene technology].

The most important concern of this contribution is the question of whether the first officially approved somatic gene therapy experiments in Switzerland (1995) are theologically and ethically justified. On the basis of a christian concept of the dignity of human life this question is taken up with regard to acknowledged, relevant medical principles. The answer, which is basically positive, is nevertheless bound to a series of conditions that are presently indispensable. The second part of the article briefly develops ethical postulates concerning further issues in the discussion on human gene technology (research and production of medicines, genome analysis, so-called predictive medicine, data protection, and effects upon the understanding of health and disease).

Ethics, Medical↗

Reflections on the cost consequences of the new gene technology for health policy.

This article presents a preliminary and necessarily tentative and subjective assessment of the impact of new gene technology on health care costs. In the short term, diagnosis and treatment of genetic disease are likely to increase costs. Treatment with nongene therapy will continue to be far less expensive than gene therapy where it is available. Research developments to monitor as indicators of forthcoming cost reductions in genetic therapy are set forth. Some forms of genetic screening may soon reduce health care costs, and an example is provided. Genetically engineered pharmaceuticals are described and their impact on costs reviewed. Conditions under which they are likely to reduce health care costs are indicated.

Biotechnology↗

[Gene technology in immunologic research, diagnosis and treatment].

T- and B-lymphocytes recognize foreign material (antigens) by means of specific receptors. After the antigen-specific recognition, lymphocytes and other cells communicate both through membrane-bound and soluble signal molecules. Gene technology has enabled mapping and sequencing of several genes which encode receptor or signal molecules. Gene sequencing has provided essential new information on the structure of receptor and signal molecules, and has thus formed the basis for our rapidly growing knowledge of the physiology and pathophysiology of the immune system. Molecular genetics has also produced techniques which are already being used in the diagnosis of immunologic diseases, and which can possibly be used therapeutically in gene transplantation of various immune defects.

Animals↗

The realness of risk: gene technology in Germany.

This paper examines the material relations of risk within a dispute about the hazards of manufacturing human insulin using gene technology, and the rôle played by the referent 'real risk' in the technical performance of risk in that dispute. It draws on recent work in science and technology studies that extends actor-network theory to examine the performance of reality in scientific practice. The multiplicity of risks in the dispute, and the links made and unmade between them, are examined. I argue that in the dispute, risks were contingently linked and separated around a referent 'real risk' that emerged within the recombinant DNA debate of the late 1970s. I contrast my account of risk with realist and relativist accounts, each of which values risk as an abstract entity. In my account, risk's value is contingent upon sets of material relations that link hazards and procedures for their minimization. Risk's realness emerges as some risks are linked and others separated, working a multiple/singular relation in an ontological politics of risk.

Genetics↗

Democracy and the governance of uncertainty. The case of agricultural gene technologies.

The use of genetically modified organisms (GMOs) in agriculture and food production is the object of an intense and divisive debate. Drawing on a study on the public perception of agricultural gene technologies carried out in five European countries, the article deals with the policy aspects of the issue, and more precisely on the relation between institutions, experts and the public in a context of deep uncertainty. A theoretical framework is developed and compared with the study findings, suggesting that issues like the GMOs one represent a strong case for a more participatory policy-making. My conclusions suggest a style of governance based on the principles of deliberative democracy, as a suitable approach to the confrontation of different viewpoints and forms of knowledge. This appears to be the best way to improve the overall quality of policy-making: in this I include its legitimacy, the degree of public trust, and also the actual quality of its products. Strengthening the role of the public sphere seems more effective than simply increasing direct decision-making by the populace, and it offers an alternative to the 'elitist' solutions to the crisis of representative democracy.

Agriculture↗

[Gene technology and mental disorders].

The article briefly reviews the use of modern molecular genetic methods in research into the genetic bases of psychiatric diseases. It raises some basic methodological problems, and describes more recent technologies (RFLP/VNTR markers). Present knowledge about the molecular genetics of Alzheimer's disease, schizophrenia, manic depression, Tourette's syndrome and infantile autism is briefly reviewed in to order show the potential benefits of gene technological methods in this area of research.

Genetic Markers↗