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PubMed2002

Risk assessment for release of genetically modified organisms: a virus to reduce the fertility of introduced wild mice, Mus domesticus.

Risk assessment is a key task in developing genetically modified organisms (GMOs) intended for release into the environment. A risk assessment protocol is described, focusing on genetically modified biological control agents intended to reduce fertility in mammalian pests. The protocol is being applied to development of an immunocontraceptive murine cytomegalovirus vaccine intended to reduce the frequency and extent of costly troublesome plagues of introduced house mice, Mus domesticus, in southern Australia. Success of the agent, including regulatory approval for release to target populations, will depend on demonstrated biosafety, on the biophysical consequences of releasing the agent, and on public perceptions of the consequences and ongoing risks. The proposed risk assessment protocol addresses biosafety and the biophysical and social risks. It elicits perceptions of interaction and risk from the project scientists and from representatives of interested or affected sectors of society. The perceptions are documented for examination interactively in subsequent socially inclusive formal risk assessments. Representatives of the relevant social sectors participate with the scientists, iteratively if needed, in a workshop to assess the risks of releasing the particular GMO into the environment, using a formal inductive procedure, GENHAZ, designed specifically for assessment and management of the risks of GMOs. Use of this protocol is intended to precede and complement risk assessment and risk management procedures specified by gene technology legislation and regulations.

Animals↗
PubMed1998

Effect of genetically modified, low-phytic acid maize on absorption of iron from tortillas.

BACKGROUND: Genetically modified, low-phytic acid strains of maize were developed to enhance mineral absorption, but have not been tested previously in humans. OBJECTIVES: We evaluated the mineral and phytic acid contents of a low-phytic acid "flint" maize (LPM, the lpa-1-1 mutant) and its parent, wild-type strain (WTM) and measured iron absorption from tortillas prepared with each type of maize and from a reference dose of ferrous ascorbate. DESIGN: Proximate composition and mineral and phytic acid contents were measured by standard techniques. Iron absorption from tortillas was evaluated by using the extrinsic tag method and was measured as the incorporation of radiolabeled iron into the red blood cells of 14 nonanemic men 2 wk after intake. RESULTS: The phytic acid content of LPM was 3.48 mg/g, approximately 35% of the phytic acid content of WTM; concentrations of macronutrients and most minerals were not significantly different between strains. Iron absorption results were adjusted to 40% absorption of ferrous ascorbate. Iron absorption was 49% greater from LPM (8.2% of intake) than from WTM (5.5% of intake) tortillas (P < 0.001, repeated-measures analysis of variance). CONCLUSION: Consumption of genetically modified, low-phytic acid strains of maize may improve iron absorption in human populations that consume maize-based diets.

Adult↗
PubMed2006

Unintended effects in genetically modified crops: revealed by metabolomics?

In Europe the commercialization of food derived from genetically modified plants has been slow because of the complex regulatory process and the concerns of consumers. Risk assessment is focused on potential adverse effects on humans and the environment, which could result from unintended effects of genetic modifications: unintended effects are connected to changes in metabolite levels in the plants. One of the major challenges is how to analyze the overall metabolite composition of GM plants in comparison to conventional cultivars, and one possible solution is offered by metabolomics. The ultimate aim of metabolomics is the identification and quantification of all small molecules in an organism; however, a single method enabling complete metabolome analysis does not exist. Given a comprehensive extraction method, a hierarchical strategy--starting with global fingerprinting and followed by complementary profiling attempts--is the most logical and economic approach to detect unintended effects in GM crops.

Consumer Product Safety↗
PubMed2002

Genetically modified maize and soybean on the Egyptian food market.

The results of a survey study on food samples produced from genetically modified soybean and maize collected from the Egyptian market are presented. Forty samples of soybean and 40 samples of maize products have been gathered randomly from markets in Cairo and Giza. The genetic modification was detected by polymerase chain reaction (PCR) using official detection methods according to section 35 of the German Foodstuffs Act. Samples were investigated for the presence of material derived from the following genetically modified organisms (GMOs) all of which are approved for food use in Europe: Roundup Ready soybean (RRS) and maize lines Bt176, Bt11, T25 and MON810. In addition, samples were examined in qualitative and quantitative analysis for the presence of material derived from the transgenic maize line StarLink (Aventis) which was approved for animal feed use exclusively in the US. Twenty % of 40 investigated soy samples contained Roundup Ready soybean; 15% of 40 maize samples tested positive for Bt176 and 12.5% positive for Bt11 maize. Furthermore, the presence of StarLink maize could clearly be demonstrated in four samples mixed with Bt176 and Bt11. The percentage of StarLink was less than 1% in quantitative analysis. The maize lines T25 and MON810 were not detected.

DNA, Plant↗
PubMed1996

Implantation of autologous skin fibroblast genetically modified to secrete clotting factor IX partially corrects the hemorrhagic tendencies in two hemophilia B patients.

OBJECTIVE: To examine the safety and effects of gene therapy for hemophilia B by implantation of autologous fibroblasts genetically modified to secrete clotting factor IX (hFIX). PATIENTS AND METHODS: Two hemophilia B patients LD and LW were selected from one family to accept gene transfer study. The hFIX protein of both patients were about 100 ng/ml plasma and hFIX activity was about 2%. The autologous skin fibroblasts of the two patients were genetically modified by retrovirus-mediated gene transfer with XL-IX and N2CMVIX vector (HBSF-IX). Human hFIX protein was measured by ELISA, hFIX activity was measured by one-stage clotting assay and barium citrate sorbent method. hFIX inhibitor was assayed by Bethesda methods. Human hFIX cDNA was detected by PCR. HBSF-IX cells were mixed with collagen for injection after safety assessments. RESULTS: The HBSF-IX cells from the two patients secreted hFIX at high levels in vitro. After implantation of autologous HBSF-IX cells, no treatment-related side effects were observed. Plasma hFIX protein in both patients increased over 2 folds after several injections of HBSF-IX cells and persisted for more than 420 days. Blood clotting activity increased significantly in both patients, hemorrhagic tendencies have been partially corrected after treatment. Further elevation of hFIX can be achieved by repeating the same treatment 420 days later in Patient LD. CONCLUSIONS: Implantation of autologous fibroblast genetically modified to secrete human hFIX offers a simple, safe and effective approach to gene therapy of hemophilia B.

Adolescent↗
PubMed2002

Splicing regulation as a potential genetic modifier.

Inherited diseases are associated with profound phenotypic variability, which is affected strongly by genetic modifiers. The splicing machinery could be one such modifying system, through a mechanism involving splicing motifs and their interaction with a complex repertoire of splicing factors. Mutations in splicing motifs and changes in levels of splicing factors can result in different splicing patterns. Changes in the level of normal transcripts or in the relative pattern of different mRNA isoforms affect disease expression, leading to phenotypic variability. Here, we discuss the splicing machinery in terms of its significance in disease severity and its potential role as a genetic modifier.

Alternative Splicing↗
PubMed2006

Comparison of ileal digested production of parental rice and rice genetically modified with cowpeas trypsin inhibitor.

OBJECTIVE: To compare the ileal digestibility of protein and amino acids in parental rice and rice genetically modified with sck gene. METHODS: Six experimental swines were surgically fixed with a simple T-cannula at the terminal ileum and fed with parental rice and rice genetically modified with sck gene alternately. The ileum digesta were collected and analyzed for determination of apparent and true digestibility of protein and amino acids. RESULTS: The apparent and true digestibility of protein was similar in these two types of rice. Except for the apparent digestibility of lysine, there was no difference in the apparent and true digestibility of the other 17 amino acids. CONCLUSION: The digestibility of protein and amino acids is not changed by the insertion of foreign gene, so it can meet the request of "substantial equivalence" in digestibility of protein and amino acids.

Amino Acids↗
PubMed2006

Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model.

OBJECTIVE: Gene transfer to hematopoietic stem cells has recently been demonstrated to benefit a small number of patients in whom a selective advantage is conferred upon genetically modified cells; however, in disorders where no such selective advantage is conferred, conditioning appears necessary to allow adequate engraftment. To decrease the toxicity profile, we sought to develop nonmyeloablative conditioning regimens and in this work, explored the use of intravenous busulfan in a large animal model. METHODS: Busulfan pharmacokinetics and toxicity were monitored in young rhesus macaques at two dosing levels (4 and 6 mg/kg). These doses were then employed to condition two animals at each dose level prior to autologous transplantation of genetically modified cells using our standard methods. RESULTS: Busulfan pharmacokinetic (PK) data showed the area under the curve (AUC), drug half-life, and drug clearance were consistent within each dose group and similar to those reported in children. Single doses of busulfan were well tolerated and produced dose-dependent myelosuppression, most notably in the neutrophil and platelet counts. Although marking levels reached over 1% early in one animal, the long-term marking was low but detectable at 0.01 to 0.001%. CONCLUSIONS: We conclude that low-dose intravenous bolus infusion of busulfan is well tolerated, has dose-dependent effects on peripheral blood counts, and allows long-term engraftment of genetically modified cells, but at levels too low for most clinical disorders.

Animals↗
PubMed2003

Communicating about the risks and benefits of genetically modified foods: the mediating role of trust.

Recent research suggests that public attitudes toward emerging technologies are mainly driven by trust in the institutions promoting and regulating these technologies. Alternative views maintain that trust should be seen as a consequence rather than a cause of such attitudes. To test its actual role, direct as well as mediating effects of trust were tested in an attitude change experiment involving 1,405 consumers from Denmark, Germany, Italy, and the United Kingdom. After prior attitudes to genetic modification in food production had been assessed, participants received different information materials (either product-specific information or balanced/general information about genetic modification in food production) and were asked to evaluate different types of genetically modified foods (either beer or yoghurt). The information materials were attributed to different information sources (either an industry association, a consumer organization, or a government source). After completion, perceived risk and perceived benefit were assessed, and participants indicated their trust in the information sources to which the materials had been attributed. Direct and trust-mediated attitude change effects were estimated in a multi-sample structural equation model. The results showed that information provision had little effect on people's attitudes toward genetically modified foods, and that perceptions of information source characteristics contributed very little to attitude change. Furthermore, the type of information strategy adopted had almost no impact on postexperimental attitudes. The extent to which people trusted the information sources appeared to be driven by people's attitudes to genetically modified foods, rather than trust influencing the way that people reacted to the information. Trust was not driving risk perception-rather, attitudes were informing perceptions of the motivation of the source providing the information.

Attitude↗
PubMed2000

Enhanced vascularization of cultured skin substitutes genetically modified to overexpress vascular endothelial growth factor.

Cultured skin substitutes have been used as adjunctive therapies in the treatment of burns and chronic wounds, but they are limited by lack of a vascular plexus. This deficiency leads to greater time for vascularization compared with native skin autografts and contributes to graft failure. Genetic modification of cultured skin substitutes to enhance vascularization could hypothetically lead to improved wound healing. To address this hypothesis, human keratinocytes were genetically modified by transduction with a replication incompetent retrovirus to overexpress vascular endothelial growth factor, a specific and potent mitogen for endothelial cells. Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates inoculated with human fibroblasts and either vascular endothelial growth factor-modified or control keratinocytes were prepared, and were cultured in vitro for 21 d. Northern blot analysis demonstrated enhanced expression of vascular endothelial growth factor mRNA in genetically modified keratinocytes and in cultured skin substitutes prepared with modified cells. Furthermore, the vascular endothelial growth factor-modified cultured skin substitutes secreted greatly elevated levels of vascular endothelial growth factor protein throughout the entire culture period. The bioactivity of vascular endothelial growth factor protein secreted by the genetically modified cultured skin substitutes was demonstrated using a microvascular endothelial cell growth assay. Vascular endothelial growth factor-modified and control cultured skin substitutes were grafted to full-thickness wounds on athymic mice, and elevated vascular endothelial growth factor mRNA expression was detected in the modified grafts for at least 2 wk after surgery. Vascular endothelial growth factor-modified grafts exhibited increased numbers of dermal blood vessels and decreased time to vascularization compared with controls. These results indicate that genetic modification of keratinocytes in cultured skin substitutes can lead to increased vascular endothelial growth factor expression, which could prospectively improve vascularization of cultured skin substitutes for wound healing applications.

Animals↗
PubMed2004

Genetically modified animal models as tools for studying bone and mineral metabolism.

Genetic modification of mice is a powerful tool for the study of bone development and metabolism. This review discusses the advantages and disadvantages of various approaches used in bone-related research and the contributions these studies have made to bone biology. Genetic modification of mice is a powerful tool for the study of bone development and metabolism. This review discusses the advantages and disadvantages of various approaches used in bone-related research and the contributions these studies have made to bone biology. The approaches to genetic modification included in this review are (1) overexpression of genes, (2) global gene knockouts, (3) tissue-specific gene deletion, and (4) gene knock-in models. This review also highlights issues that should be considered when using genetically modified animal models, including the rigorous control of genetic background, use of appropriate control lines, and confirmation of tissue specificity of gene expression where appropriate. This technology provides a unique and powerful way to probe the function of genes and is already revolutionizing our approach to understanding the physiology of bone development and metabolism.

Animals↗
PubMedDate not supplied

Genetically modified PC12 brain grafts: survivability and inducible nerve growth factor expression.

Neural transplantation of genetically modified cells has been successfully employed to reverse functional deficits in animal models of neurodegenerative disorders, including Parkinson's disease. While implanted PC12 cells secrete dopamine in vivo and can ameliorate dopamine deficiency in parkinsonian rat model systems, these cells either degenerate within 2-3 wk postimplantation (presumably due to the lack of neural trophic factor support at the site of implantation), or in some cases, form a tumor mass leading to the death of the host animal. To address these limitations, we have developed a genetically modified PC12 cell line that can synthesize nerve growth factor (NGF) under the control of a zinc-inducible metallothionein promoter. When implanted in the rat striatum and under in vivo zinc stimulation, these cells will neuro-differentiate, express tyrosine hydroxylase, and will undergo survival through potential autocrine trophic support. This regulatable cell line and general approach may provide additional insight on the potential utilization of cell transplants for treatment of Parkinson's disease and other neurodegenerative disorders.

Animals↗
PubMed2003

Repeated introduction of genetically modified Pseudomonas putida WCS358r without intensified effects on the indigenous microflora of field-grown wheat.

To investigate the impact of genetically modified, antibiotic-producing rhizobacteria on the indigenous microbial community, Pseudomonas putida WCS358r and two transgenic derivatives were introduced as a seed coating into the rhizosphere of wheat in two consecutive years (1999 and 2000) in the same field plots. The two genetically modified microorganisms (GMMs), WCS358r::phz and WCS358r::phl, constitutively produced phenazine-1-carboxylic acid (PCA) and 2,4-diacetylphloroglucinol (DAPG), respectively. The level of introduced bacteria in all treatments decreased from 10(7) CFU per g of roots soon after sowing to less than 10(2) CFU per g after harvest 132 days after sowing. The phz and phl genes remained stable in the chromosome of WCS358r. The amount of PCA produced in the wheat rhizosphere by WCS358r::phz was about 40 ng/g of roots after the first application in 1999. The DAPG-producing GMMs caused a transient shift in the indigenous bacterial and fungal microflora in 1999, as determined by amplified ribosomal DNA restriction analysis. However, after the second application of the GMMs in 2000, no shifts in the bacterial or fungal microflora were detected. To evaluate the importance of the effects induced by the GMMs, these effects were compared with those induced by crop rotation by planting wheat in 1999 followed by potatoes in 2000. No effect of rotation on the microbial community structure was detected. In 2000 all bacteria had a positive effect on plant growth, supposedly due to suppression of deleterious microorganisms. Our research suggests that the natural variability of microbial communities can surpass the effects of GMMs.

Crops, Agricultural↗
PubMed2003

Presence of potential allergy-related linear epitopes in novel proteins from conventional crops and the implication for the safety assessment of these crops with respect to the current testing of genetically modified crops.

Mitochondria of cytoplasmic male sterile crop plants contain novel, chimeric open reading frames. In addition, a number of crops carry endogenous double-stranded ribonucleic acid (dsRNA). In this study, the novel proteins encoded by these genetic components were screened for the presence of potential binding sites (epitopes) of allergy-associated IgE antibodies, as was previously done with transgenic proteins from genetically modified crops. The procedure entails the identification of stretches of at least six contiguous amino acids that are shared by novel proteins and known allergenic proteins. These stretches are further checked for potential linear IgE-binding epitopes. Of the 16 novel protein sequences screened in this study, nine contained stretches of six or seven amino acids that were also present in allergenic proteins. Four cases of similarity are of special interest, given the predicted antigenicity of the identical stretch within the allergenic and novel protein, the IgE-binding by a peptide containing an identical stretch reported in literature, or the multiple incidence of identical stretches of the same allergen within a novel protein. These selected stretches are present in novel proteins derived from oilseed rape and radish (ORF138), rice (dsRNA), and fava bean (dsRNA), and warrant further clinical testing. The frequency of positive outcomes and the sizes of the identical stretches were comparable to those previously found for transgenic proteins in genetically modified crops. It is discussed whether novel proteins from conventional crops should be subject to an assessment of potential allergenicity, a procedure which is currently mandatory for transgenic proteins from genetically modified crops.

Journal Article↗
PubMed2005

Multiplex polymerase chain reaction and ligation detection reaction/universal array technology for the traceability of genetically modified organisms in foods.

A multiplex polymerase chain reaction (PCR) system was developed for the simultaneous detection of target sequences in genetically modified soybean (Roundup Ready) and maize (MON810, Bt176, Bt11, and GA21). Primer pairs were designed to amplify the junction regions of the transgenic constructs analyzed and the endogenous genes of soybean (lectin) and maize (zein) were included as internal control targets to assess the efficiency of all reactions. This multiplex PCR has constituted the basis for an efficient platform for genetically modified organism traceability based on microarray technology. In particular, the ligation detection reaction combined to a universal array approach, using the multiplex PCR as target, was applied. High specificity and sensitivity were obtained.

DNA, Plant↗
PubMed2002

Approaches to assessment of the allergenic potential of novel proteins in food from genetically modified crops.

The safety assessment of food derived from genetically modified plants continues to attract considerable attention. Among the important issues that need to be considered is whether the products of novel genes introduced into crop plants will have the potential to induce allergic sensitization or to elicit allergic disease. Hierarchical approaches to allergenicity testing have been proposed, and these incorporate evaluation of the structural and sequence homology and serological identity of novel proteins with known allergens, measurement of resistance to proteolytic digestion, and assessment of allergenic potential using animal models. Accounts of these approaches are available elsewhere, and it is not the purpose of this article to provide a detailed critique of specific methods. Our intention is rather to look more broadly at the strategy for assessment of allergenic potential, the challenges such assessments pose for the practicing toxicologist, and how some of these might best be addressed.

Allergens↗
PubMed2000

Genetically modified crops: methodology, benefits, regulation and public concerns.

The genetic modification of crop plants from the methodology involved in their production through to the current debate on their use in agriculture are reviewed. Techniques for plant transformation by Agrobacterium tumefaciens and particle bombardment, and for the selection of transgenic plants using marker genes are described. The benefits of currently available genetically modified (GM) crops in reducing waste and agrochemical use in agriculture, and the potential of the technology for further crop improvement in the future are discussed. The legal requirements for containment of novel GM crops and the roles of relevant regulatory bodies in ensuring that GM crops and food are safe are summarized. Some of the major concerns of the general public regarding GM crops and food: segregation of GM and non-GM crops and cross-pollination between GM crops and wild species, the use of antibiotic resistance marker genes, the prevention of new allergens being introduced in to the food chain and the relative safety of GM and non-GM foods are considered. Finally, the current debate on the use of GM crops in agriculture and the need for the government, scientists and industry to persevere with the technology in the face of widespread hostility is studied.

Consumer Product Safety↗