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At least 73 records · Page 4Linked to original sources
PubMed2005

Investigations on the reaction pattern of photosystem II in leaves from Arabidopsis thaliana wild type plants and mutants with genetically modified lipid content.

The role of digalactosyldiacylglycerol (DGDG) for the functional competence of photosystem II (PS II) has been analyzed in leaves of Arabidopsis thaliana plants where the lipid composition was selectively modified by genetic mutations. Measurements with a newly developed laser flash fluorometer and data evaluation within the framework of an extended "3-quencher" model lead to the following results: (i) the normalized fluorescence transients F(t)/F(0) induced by an actinic laser flash in dark adapted leaves are virtually the same in wild type (WT) and mutants with diminished (about 50%) monogalactosyldiacylglycerol (MGDG) content (mgd1 mutant); (ii) significant changes of the F(t)/F(0) curves are observed in mutants with a severely reduced DGDG content; (iii) in mutants dgd1 and dgd1 dgd2-1 with DGDG contents of 1/15 of the control and below the detection limit, respectively, the probability of the dissipative recombination reaction between P680(+)(*) and Q(A)(-) increases by factors of about two and four, respectively; (iv) the acceptor side reactions are only slightly affected; (v) excitation with actinic laser flash energies above the saturation level of photosynthesis gives rise to elevated carotenoid triplet formation in mutants dgd1 and dgd1 dgd2-1; and (vi) the relationship between DGDG content and functional effect(s) on PS II is strikingly nonlinear. A small fraction of DGDG molecules of the total pool is inferred to be specifically bound to PS II as an essential constituent for its functional competence.

Arabidopsis↗
PubMed1998

Intraspinal grafting of fibroblasts genetically modified by recombinant adenoviruses.

Intracerebral or intraspinal grafting of genetically modified primary fibroblasts has been shown to enhance functional recovery in several models of CNS disease, including spinal cord injury. Most of these studies utilized retrovirus vectors. In this report, we describe in vitro conditions for genetically modifying primary fibroblasts with recombinant adenovirus vectors carrying the lacZ or green fluorescent protein (GFP) genes. As intraspinal allografts in animals immunosuppressed by cyclosporin A, the genetically modified cells survived and expressed the transgenes for at least 2 months. We conclude that recombinant adenovirus vectors are efficient and convenient tools for ex vivo gene therapy in the CNS.

Adenoviridae↗
PubMed1999

A system for the propagation of adenoviral vectors with genetically modified receptor specificities.

The development of genetically modified adenovirus (Ad) vectors with specificity for a single cell type will require both the introduction of novel tropism determinants and the ablation of endogenous tropism. Consequently, it will not be possible to exploit the native cellular entry pathway in the propagation of these targeted Ad vectors. Based on the concept that Ad enters cells by a two-step process in which a primary receptor serves as a high affinity binding site for the Ad fiber knob, with subsequent internalization mediated by alpha v integrins, we designed two artificial primary receptors. The extracellular domain of one of these synthetic receptors was derived from a single-chain antibody (sFv) with specificity for Ad5 knob, while the second receptor consisted of an icosapeptide identified by biopanning a phage display library against Ad5 knob. Expression of either of these artificial virus-binding receptors in fiber receptor-negative cells possessing alpha v integrins conferred susceptibility to Ad infection. We then created a novel mechanism for cell binding by genetically modifying both the vector and the target cell. In this approach, six histidine (His) residues were incorporated at the C-terminal of the Ad fiber protein. The resultant Ad vector was able to infect nonpermissive cells displaying the cognate artificial receptor, containing an anti-His sFv. This strategy, comprising a genetically engineered Ad virion and a modified cell line, should be useful in the propagation of targeted Ad vectors that lack the ability to bind the native fiber receptor.

Adenoviridae↗
PubMedDate not supplied

Presentation of tumor antigens by dendritic cells genetically modified with viral and nonviral vectors.

Genetic modification of dendritic cells (DCs) with recombinant vectors encoding tumor antigens may aid in developing new immunotherapeutic treatments for patients with cancer. Here, we characterized antigen presentation by human DCs genetically modified with plasmid cDNAs, RNAs, adenoviruses, or retroviruses, encoding the melanoma antigen gp100 or the tumor-testis antigen NY-ESO-1. Monocyte-derived DCs were electroporated with cDNAs or RNAs, or transduced with adenoviruses. CD34+ hematopoietic stem cell-derived DCs were used for retroviral transduction. Genetically modified DCs were coincubated with CD8+ and CD4+ T cells that recognized major histocompatibility complex class I- and class II-restricted epitopes from gp100 and NY-ESO-1, and specific recognition was evaluated by interferongamma secretion. Cytokine release by both CD8+ and CD4+ T cells was consistently higher in response to DCs modified with adenoviruses than cDNAs or RNAs, and maturation of DCs after genetic modification did not consistently alter patterns of recognition. Also, retrovirally transduced DCs encoding gp100 were well recognized by both CD8+ and CD4+ T cells. These data suggest that DCs transduced with viral vectors may be more efficient than DCs transfected with cDNAs or RNAs for the induction of tumor reactive CD8+ and CD4+ T cells in vitro and in human vaccination trials.

Adenoviridae↗
PubMed1993

Evaluating the fate of genetically modified microorganisms in the environment: are they inherently less fit?

Genetically modified microorganisms hold great promise for environmental applications. Nonetheless, some may have unintended adverse effects. Of particular concern for risk assessment is the simple fact that microorganisms are self-replicating entities, so that it may be impossible to control an adverse effect simply by discontinuing further releases of the organism. It has been suggested, however, that genetically modified microorganisms will be poor competitors and therefore unable to persist in the wild due to energetic inefficiency, disruption of genomic coadaptation, or domestication. Many studies support the hypothesis that genetically modified microorganisms are less fit than their progenitors, but there are a few noteworthy counter-examples in which genetic modifications unexpectedly enhance competitive fitness. Furthermore, subsequent evolution may eliminate the maladaptive effects of some genes, increasing the likelihood that a modified organism or its engineered genes will persist. Evaluating the likelihood that a genetically modified microorganism or its engineered genes will persist is a complex ecological and evolutionary problem. Therefore, an efficient regulatory framework would require such evaluations only when there are plausible scenarios for significant adverse environmental effects.

Bacteria↗
PubMed2005

Health considerations regarding horizontal transfer of microbial transgenes present in genetically modified crops.

The potential effects of horizontal gene transfer on human health are an important item in the safety assessment of genetically modified organisms. Horizontal gene transfer from genetically modified crops to gut microflora most likely occurs with transgenes of microbial origin. The characteristics of microbial transgenes other than antibiotic-resistance genes in market-approved genetically modified crops are reviewed. These characteristics include the microbial source, natural function, function in genetically modified crops, natural prevalence, geographical distribution, similarity to other microbial genes, known horizontal transfer activity, selective conditions and environments for horizontally transferred genes, and potential contribution to pathogenicity and virulence in humans and animals. The assessment of this set of data for each of the microbial genes reviewed does not give rise to health concerns. We recommend including the above-mentioned items into the premarket safety assessment of genetically modified crops carrying transgenes other than those reviewed in the present study.

Journal Article↗
PubMed2006

The program for phenotyping of genetically modified animals at AstraZeneca.

Genetically modified mice offer a wide range of possibilities in preclinical drug discovery, e.g. for use in target identification, target validation and disease model generation. However, genomic modification and alteration in gene expression may cause unpredicted phenotypic alterations in the organism other than the intended ones. The aim of this study was to determine the importance of establishing the phenotype of transgenic and knockout mice models for use in pharmaceutical research. A total number of 51 mouse models (transgenic and knockout) produced at AstraZeneca during a 4 year period were subjected to a thorough phenotyping package covering clinical as well as morphological aspects. Phenotype abnormalities were recorded in 36 (70.6%) of the mouse models. The majority of findings were considered to be minor in magnitude. Histopathological changes related to the genotype of the animals were observed in 33% of the mouse models, underlining the importance of pathology in the phenotyping program.

Animals↗
PubMed1994

Efficient repopulation of denuded rabbit arteries with autologous genetically modified endothelial cells.

BACKGROUND: In an effort to determine whether specific genetic modifications of cells of the vascular system might improve the efficacy of existing clinical procedures such as endarterectomy, atherectomy, and percutaneous angioplasty, we investigated the utility of gene transfer to rapidly and efficiently repopulate injured arteries with genetically modified cells in an animal model. METHODS AND RESULTS: The method involves the harvest of autologous venous-derived endothelial cells, the efficient genetic modification of the cells through the use of recombinant retroviruses, and the subsequent implantation of the genetically modified cells on the surface of balloon-denuded arterial segments. With a rabbit model, freshly isolated endothelial cells were transduced with a recombinant retrovirus encoding the bacterial enzyme beta-galactosidase. The autologous transduced cells were then implanted on the surface of balloon-denuded ileofemoral arterial segments at different cell densities; after 1 to 14 days, the animals were killed, and the vessel segments were examined. Cells expressing the bacterial gene product, as determined by in situ staining for beta-galactosidase, were found to be present on the surface of 28 of the 32 arteries seeded with genetically modified cells. Vessels examined at 4 to 7 days after seeding displayed 40% to 90% coverage with transduced cells, even when seeded at subconfluent density, and an intact endothelial cell monolayer, as evidenced by scanning electron microscopy studies. Vessels examined at 14 days after seeding revealed more variable staining for beta-galactosidase yet, again, in most cases, an intact endothelial cell monolayer. CONCLUSIONS: These studies indicate the feasibility of generating segments of arterial vessels containing genetically modified cells in a rapid and efficient fashion. Further studies are now necessary to determine whether the local expression of specific polypeptides within a region of vessel for a finite period of time will be clinically useful.

Animals↗
PubMed2006

Invasion of pests resistant to Bt toxins can lead to inherent non-uniqueness in genetically modified Bt-plant dynamics: mathematical modeling.

Genetically modified crops are effective pest management tools for worldwide growers. However, there is a concern that pests may develop resistance to Bt-toxins produced by genetically modified Bt-plants. We study the impact of the Bt-resistant pests on Bt-crops. Furthermore, the dynamics of the Bt-plant-Bt-susceptible insects-Bt-resistant insects system is analysed and it is shown that throughout the insect reproduction period the plant biomass dynamics resulting from invasion of Bt-resistant insects is non-unique. Namely, the chaotic attractor and the limit cycle, which are responsible for the plant and insect biomass dynamics, are shown to coexist. As a result, the Bt-plant-Bt-resistant insect system can manifest either chaotic or regular oscillations of plant and insect biomass depending on spatial patterns resulting from invasion of Bt resistant insects into the Bt plant-Bt susceptible insect system. We show that the non-uniqueness of the system dynamics under unfavorable environmental conditions, such as in the so-called zones of risky agriculture in many developing countries and industrialized countries, can lead to essential decrease in the plant biomass.

Animals↗
PubMed2000

Growing-finishing performance and carcass characteristics of pigs fed normal and genetically modified low-phytate corn.

A genetically modified corn hybrid homozygous for the lpa1 allele, containing low phytate (LP), and its nearly isogenic equivalent hybrid (normal) were compared in two experiments with growing-finishing swine. In Exp. 1, 210 barrows (27 kg) were allotted to one of six dietary treatments with two corn hybrids (LP and normal) and three P feeding regimens. There were five replicate pens (seven pigs/pen) per treatment. Treatments consisted of diets that were supplemented with P throughout the growing-finishing period (.2% P and .15% supplemental P during growing and finishing phases, respectively) or only during the growing phase (.2% supplemental P) or that were not supplemented with P throughout the growing-finishing period. Performance at the end of the growing phase was based on a 2 x 2 factorial arrangement of treatments with two corn hybrids and two levels of added P (0 and .2%). This resulted in 10 replicates for the treatments supplemented with .2% P. The finishing phase (73 to 112 kg) was a 2 x 3 factorial arrangement of treatments with the two types of corn and three regimens of added P during the finishing period. Breaking load (BL) and ash of the fourth metacarpal were evaluated from one pig/pen at the end of the growing phase and from all pigs after slaughter. Pigs fed the LP corn diet without added P had greater body weight gain, feed efficiency, BL, and ash content of the fourth metacarpal than pigs fed the normal corn diet without added P. Performance was similar between pigs fed the LP diet without added P and pigs fed LP and normal corn with added P. In Exp. 2, 1,092 gilts (34 kg body weight) were allotted by weight in a commercial facility to one of three treatments: 1) normal corn/soybean meal diet containing .29% and .22% available P during the growing and finishing phases, respectively; 2) LP corn/soybean meal diet with the same available P level as Treatment 1; and 3) same as Treatment 2 for 8 wk, then no inorganic P supplementation during the finishing phase. All pigs were slaughtered at approximately 122 kg. There were no significant differences in growing-finishing performance or BL among treatments. However, pigs fed diets containing LP corn possessed carcasses with less backfat and a higher percentage of lean (P < .01). These results confirm that the P in LP corn is available to the pig and suggest that pigs fed diets containing this genetically modified corn will have more desirable carcasses.

Animal Feed↗
PubMed2000

An analytical approach to the implementation of genetically modified crops.

Public scepticism towards genetically modified (GM) crops is increasing. To address this, the risks and benefits of GM crops must be examined across scientific disciplines, and be discussed with the authorities, the agricultural industry and the consumers. In a feasibility study we have systematically analysed the challenges of the development and marketing of GM crops in Europe. A life-cycle inventory was used together with established technology foresight techniques in an interdisciplinary and empirical framework. The approach taken in this study established a dialogue between stakeholders and provided a framework for discussions about the future direction of GM crops.

Agriculture↗
PubMed2002

Safety assessment of genetically modified crops.

The development of genetically modified (GM) crops has prompted widespread debate regarding both human safety and environmental issues. Food crops produced by modern biotechnology using recombinant techniques usually differ from their conventional counterparts only in respect of one or a few desirable genes, as opposed to the use of traditional breeding methods which mix thousands of genes and require considerable efforts to select acceptable and robust hybrid offspring. The difficulties of applying traditional toxicological testing and risk assessment procedures to whole foods are discussed along with the evaluation strategies that are used for these new food products to ensure the safety of these products for the consumer.

Animals↗
PubMed2005

Comparison of tuber proteomes of potato varieties, landraces, and genetically modified lines.

Crop improvement by genetic modification remains controversial, one of the major issues being the potential for unintended effects. Comparative safety assessment includes targeted analysis of key nutrients and antinutritional factors, but broader scale-profiling or "omics" methods could increase the chances of detecting unintended effects. Comparative assessment should consider the extent of natural variation and not simply compare genetically modified (GM) lines and parental controls. In this study, potato (Solanum tuberosum) proteome diversity has been assessed using a range of diverse non-GM germplasm. In addition, a selection of GM potato lines was compared to assess the potential for unintended differences in protein profiles. Clear qualitative and quantitative differences were found in the protein patterns of the varieties and landraces examined, with 1,077 of 1,111 protein spots analyzed showing statistically significant differences. The diploid species Solanum phureja could be clearly differentiated from tetraploid (Solanum tuberosum) genotypes. Many of the proteins apparently contributing to genotype differentiation are involved in disease and defense responses, the glycolytic pathway, and sugar metabolism or protein targeting/storage. Only nine proteins out of 730 showed significant differences between GM lines and their controls. There was much less variation between GM lines and their non-GM controls compared with that found between different varieties and landraces. A number of proteins were identified by mass spectrometry and added to a potato tuber two-dimensional protein map.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2001

Effect of genetically modified Pseudomonas putida WCS358r on the fungal rhizosphere microflora of field-grown wheat.

We released genetically modified Pseudomonas putida WCS358r into the rhizospheres of wheat plants. The two genetically modified derivatives, genetically modified microorganism (GMM) 2 and GMM 8, carried the phz biosynthetic gene locus of strain P. fluorescens 2-79 and constitutively produced the antifungal compound phenazine-1-carboxylic acid (PCA). In the springs of 1997 and 1998 we sowed wheat seeds treated with either GMM 2, GMM 8, or WCS358r (approximately 10(7) CFU per seed), and measured the numbers, composition, and activities of the rhizosphere microbial populations. During both growing seasons, all three bacterial strains decreased from 10(7) CFU per g of rhizosphere sample to below the limit of detection (10(2) CFU per g) 1 month after harvest of the wheat plants. The phz genes were stably maintained, and PCA was detected in rhizosphere extracts of GMM-treated plants. In 1997, but not in 1998, fungal numbers in the rhizosphere, quantified on 2% malt extract agar (total filamentous fungi) and on Komada's medium (mainly Fusarium spp.), were transiently suppressed in GMM 8-treated plants. We also analyzed the effects of the GMMs on the rhizosphere fungi by using amplified ribosomal DNA restriction analysis. Introduction of any of the three bacterial strains transiently changed the composition of the rhizosphere fungal microflora. However, in both 1997 and 1998, GMM-induced effects were distinct from those of WCS358r and lasted for 40 days in 1997 and for 89 days after sowing in 1998, whereas effects induced by WCS358r were detectable for 12 (1997) or 40 (1998) days. None of the strains affected the metabolic activity of the soil microbial population (substrate-induced respiration), soil nitrification potential, cellulose decomposition, plant height, or plant yield. The results indicate that application of GMMs engineered to have improved antifungal activity can exert nontarget effects on the natural fungal microflora.

Antifungal Agents↗
PubMedDate not supplied

Validation of an immunoassay for detection and quantitation of a genetically modified soybean in food and food fractions using reference materials: interlaboratory study.

An immunoassay for detection of a specific genetically modified soybean (Roundup-Ready) was validated on dried soybean powder in an interlaboratory study. Different percentages of genetically modified soybeans in nonmodified soybean matrix were evaluated in a blind study. Thirty-eight laboratories from 13 countries participated. The immunoassay was evaluated for 2 endpoints: (1) To give a semiquantitative result, i.e., determination of a given sample above or below a given threshold, or (2) to compute a quantitative result, i.e., percentage of genetically modified soybeans in the sample. Semiquantitative results showed that a given sample which contained <2% genetically modified soybeans was identified as below 2% with a 99% confidence level. Quantitative use of the assay resulted in a repeatability (r) and reproducibility (R) that were computed to be RSDr = 7% and RSDR = 10%, respectively, for a sample containing 2% genetically modified soybeans. Application of this method depends on availability of appropriate reference materials for a specific food matrix. Only matrix-matched reference materials can be used for analysis of food or food fractions.

Antibodies, Monoclonal↗
PubMed1990

Rescue of basal forebrain cholinergic neurons after implantation of genetically modified cells producing recombinant NGF.

Mouse 3T3 fibroblasts were genetically modified by transfection with a mammalian expression vector containing the rat beta-nerve growth factor (NGF) gene. The transfected cell line, designated 3E, contains several hundred copies of the rat NGF gene and secretes high levels of biologically active NGF. Pieces of collagen gel containing the NGF-secreting 3E cells were grafted to the brains of unilaterally fimbria-fornix-lesioned rats. Grafts of the genetically modified NGF-producing cells rescued axotomized basal forebrain cholinergic neurons and significantly reduced cholinergic cell death in the medial septum as compared with rats treated with grafts of the parental 3T3 cells. Grafted fibroblast cells were detected, and rescue effects were noted up to 6 weeks after grafting. Local effects of NGF secreted by grafted cells were also seen at the gel-brain border in the form of sprouting acetylcholinesterase immunoreactive host cortical fibers. We suggest that implantation of genetically modified cells producing NGF may have therapeutic applications in rescuing damaged central cholinergic neurons in senile dementia of the Alzheimer type as well as in providing trophic support for chromaffin tissue grafts in Parkinson's disease.

Acetylcholinesterase↗
PubMed2004

[Genetically modified organisms in food--production, detection and risks].

The first genetically modified plant (GMP) was a tobacco resistant to antibiotics in 1983. In 1996, the first genetically altered crop, a delayed-ripening tomato was commercially released. In the year 2003, the estimated global area of GM crops for was 67.7 million hectares. To produce such a plant a gene of interest has to be isolated from the donor. Together with a promoter, terminator sequence and marker gene it has to be introduced into the plant cell which is then stimulated to generate a whole GMP expressing new characteristics (herbicide/insect resistance, delayed ripening). The last few months have seen a strong public debate over genetically modified organisms which has raised scientific, economic, political, and ethical issues. Some questions concerning the safety of GMPs are still to be answered, and decisions about their future should be based on scientifically validated information.

Animals↗
PubMed2006

Development and validation of a sensitive and fast chemiluminescent enzyme immunoassay for the detection of genetically modified maize.

Proteins from the Cry 1 family, in particular Cry 1Ab, are commonly expressed in genetically modified Bt maize in order to control chewing insect pests. A sensitive chemiluminescent sandwich enzyme immunoassay for the detection of Cry1Ab protein from genetically modified Bt maize has been developed and validated. A Cry1Ab protein-specific antibody was immobilized on 96- or 384-well microtiter plates in order to capture the Cry1Ab toxin in the sample; the bound toxin was then detected by employing a second anti-Cry1Ab antibody and a horseradish peroxidase-labeled anti-antibody, followed by measurement of the enzyme activity with an enhanced chemiluminescent system. The chemiluminescent assay fulfilled all the requirements of accuracy and precision and exhibited limits of detection of a few pg mL(-1) Cry1Ab (3 or 5 pg mL(-1), depending on the assay format), which are significantly lower than that achievable using conventional colorimetric detection of peroxidase activity and also represent an improvement compared to previously developed Cry1Ab immunoassays. High-throughput analysis can be performed using the 384-well microtiter plate format immunoassay, which also allows one to reduce the consumption of samples and reagents. Validation of the assay, performed by analyzing certified reference materials, proved that the immunoassay is able to detect the presence of the Cry1Ab protein in certified reference samples containing as low as 0.1% of MON 810 genetically modified Bt maize. This value is below the threshold requiring mandatory labeling of foods containing genetically modified material according to the actual EU regulation.

Bacillus thuringiensis Toxins↗