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Results for “genetic modifiers”

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At least 271 records · Page 15Linked to original sources
PubMed1999

Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus.

Malignant gliomas remain incurable with current interventions. Encouraging investigational approaches include the use of genetically modified herpes simplex-1 (HSV-1) viruses as direct cytotoxic agents. Combining attenuated HSV-1 with standard therapy, human U-87 malignant glioma xenografts grown in the hind limb or intracranially in athymic nude mice were exposed to ionizing radiation, inoculated with genetically modified HSV R3616, or received both virus and radiation. The combination of virus with fractionated ionizing radiation suggests a synergistic action and results in reduced tumor volumes and longer survivals when compared with treatment with either modality alone.

Animals↗
PubMed2004

Treatment of murine hepatocellular carcinoma using genetically modified cells to express interleukin-12.

BACKGROUND AND AIM: The majority of patients cannot benefit from the conventional curative treatments that are currently used for hepatocellular carcinoma (HCC), which remains a world health problem. Interleukin (IL)-12 is one of the most potent anti-tumor cytokines. The aim of the present study was to examine the anti-tumor effect and toxicity of intrahepatic delivery of IL-12 using an ex vivo gene therapy approach in a murine model of HCC. METHODS: Syngenic fibroblasts or MM45T-Li HCC tumor cells were genetically modified in vitro to express IL-12 using a polycistronic TFG murine IL-12 retroviral vector (TFGmIL-12) coding for both p35 and p40 murine IL-12 subunits. Hepatocellular carcinoma was generated using direct intrahepatic inoculation of the tumor cell line into the left liver lobe of BALB/c mice. RESULTS: Direct liver expression of IL-12 by the injected genetically modified tumor cells induced a marked inhibition of tumor growth. This effect was associated with an early infiltration of macrophages, and lymphocytes forming numerous intralobular foci. There was no significant liver toxicity, as shown by normal biochemical liver tests. At a later time, the intralobular foci were rare and consisted mainly of CD4+ T cells, while CD8+ T cells were present in the lobule. Intrahepatic expression of IL-12 did not modify circulating or splenic B lymphocytes or natural killer (NK) cells. The inhibition of tumor growth was maintained in nude mice even when depleted in NK cells. Importantly, in a second model, treatment of established day 7 liver tumors in BALB/c mice using direct intra-tumor injection of syngenic fibroblasts that were genetically modified to express IL-12 significantly reduced tumor size. CONCLUSION: In conclusion, these data provide evidence that experimental HCC can be efficiently and safely treated using ex vivo IL-12 gene therapy, which seems promising for future clinical studies.

Animals↗
PubMed2003

Genetically modified crops: environmental and human health concerns.

About 10,000 years ago subsistence farmers started to domesticate plants and it was only much later, after the discovery of the fundaments of genetics, those organisms were submitted to rational genetic improvement mainly by selecting of traits of interest. Breeders used appropriate gene combinations to produce new animal races, plant varieties and hybrids, as well as improved microorganisms such as yeasts. After the introduction of recombinant DNA techniques, the transfer of DNA between species belonging to different genera, families or kingdoms became possible. The release of transgenic plants has aroused debates about several aspects of the environmental and human risks that could result from the introduction of genetically modified crops. Less effort has been dedicated to evaluate the impact of transgenic plants on their associated microorganisms, some of which (e.g. nitrogen-fixing bacteria, mycorrhizal fungi and endophytic microbiota) are extremely important for the survival of the plant. Investigations have been made regarding the horizontal transfer of genetic material between transgenic plants and microorganisms and on the disturbance of useful symbiotic associations between plants and endophytic, epiphytic and rhizosphere communities. In most cases the results do no show any adverse effect of transgenic plants on autochthonous plant-associated microorganisms. Results from our laboratory show small changes caused by genetically modified endophytic bacteria on the indigenous endophytic population of the sweet orange Citrus sinensis. In tests using appropriated fungal strains preliminary results using extracts from transgenic plants indicate that these plants do not affect haploidization, mitotic crossing-over, mutation rate or chromosomal alterations.

Crops, Agricultural↗
PubMed2005

Assessing genetically modified crops to minimize the risk of increased food allergy: a review.

The first genetically modified (GM) crops approved for food use (tomato and soybean) were evaluated for safety by the United States Food and Drug Administration prior to commercial production. Among other factors, those products and all additional GM crops that have been grown commercially have been evaluated for potential increases in allergenic properties using methods that are consistent with the current understanding of food allergens and knowledge regarding the prediction of allergenic activity. Although there have been refinements, the key aspects of the evaluation have not changed. The allergenic properties of the gene donor and the host (recipient) organisms are considered in determining the appropriate testing strategy. The amino acid sequence of the encoded protein is compared to all known allergens to determine whether the protein is a known allergen or is sufficiently similar to any known allergen to indicate an increased probability of allergic cross-reactivity. Stability of the protein in the presence of acid with the stomach protease pepsin is tested as a risk factor for food allergenicity. In vitro or in vivo human IgE binding are tested when appropriate, if the gene donor is an allergen or the sequence of the protein is similar to an allergen. Serum donors and skin test subjects are selected based on their proven allergic responses to the gene donor or to material containing the allergen that was matched in sequence. While some scientists and regulators have suggested using animal models, performing broadly targeted serum IgE testing or extensive pre- or post-market clinical tests, current evidence does not support these tests as being predictive or practical. Based on the evidence to date, the current assessment process has worked well to prevent the unintended introduction of allergens in commercial GM crops.

Animals↗
PubMed1997

Genetically modified bone marrow-derived dendritic cells expressing tumor-associated viral or "self" antigens induce antitumor immunity in vivo.

The clinical application of synthetic tumor peptide-based vaccines is currently limited to patients with specified major histocompatibility complex (MHC) class I alleles. Such logistic limitations may be overcome using tumor gene-based approaches. Here we describe the effective generation of dendritic cells (DC) expressing tumor peptide-MHC complexes as a result of particle-mediated transfer of genes encoding tumor-associated antigens (TAA). Bone marrow-derived DC were transfected with plasmid DNA encoding the tumor-associated viral antigen E7 derived from human papilloma virus (HPV) 16. When applied as a vaccine, these genetically modified DC induced antigen-specific CD8+ cytotoxic T lymphocytes (CTL) in vivo and promoted the rejection of a subsequent, normally lethal challenge with an HPV 16-transformed tumor cell line. Of greatest interest, immunization of mice with syngeneic DC genetically modified to enhance their presentation of a constitutive "self" epitope derived from the tumor-suppressor gene product p53 caused a significant reduction in the in vivo growth of a chemically induced p53-positive sarcoma. These results suggest that cancer vaccines consisting of DC genetically modified to express TAA of viral or "self" origin effectively induce antitumor immunity in vivo.

Animals↗
PubMed2002

Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury.

Transplants of fibroblasts genetically modified to express BDNF (Fb/BDNF) have been shown to promote regeneration of rubrospinal axons and recovery of forelimb function when placed acutely into the injured cervical spinal cord of adult rats. Here we investigated whether Fb/BDNF cells could stimulate supraspinal axon regeneration and recovery after chronic (4 week) injury. Adult female Sprague-Dawley rats received a complete unilateral hemisection injury at the third cervical spinal cord segment (C3). Four-five weeks later the injury site was exposed and rats received transplants of unmodified fibroblasts (Fb/UM) or Fb/BDNF. Four-five weeks after transplantation, locomotor recovery was examined on a test of forelimb usage and regeneration of supraspinal axons was studied following injection of the anterograde tracer biotin dextran amine (BDA). Rubrospinal tract (RST), reticulospinal tract (ReST), and vestibulospinal tract (VST) axons regenerated into transplants of either Fb/UM or Fb/BDNF but the length of axonal growth was significantly different in the two groups. The absolute distance of ReST growth was 1.8-fold greater in Fb/BDNF than in Fb/UM and the absolute distance of growth of RST and VST axons showed a statistically significant 4-fold increase. All three types of regenerated axons occupied a greater proportional length of Fb/BDNF transplants than of Fb/UM transplants. Only VST axons extended into the host spinal cord caudal to the Fb/BDNF grafts, but these axons were sparse. Rats receiving Fb/BDNF used both forelimbs together to explore walls of a cylinder more often than rats receiving Fb/UM, indicating partial recovery of forelimb usage. These results demonstrate that fibroblasts genetically modified to express BDNF promote axon regeneration from supraspinal neurons in the chronically injured spinal cord with accompanying partial recovery of locomotor performance.

Animals↗
PubMed1999

A genetically modified recombinant tumor necrosis factor-alpha conjugated to the distal terminals of liposomal surface grafted polyethyleneglycol chains.

A genetically modified recombinant tumor necrosis factor (TNF)-alpha (rKRKTNF) was conjugated to the terminal carboxyl groups of liposome grafted polyethyleneglycol (PEG) chains. The long-circulating liposomes were composed of egg phosphatidylcholine, cholesterol (chol) and 7% carboxyl PEG-phosphatidylethanolamine. The conjugation efficiency of the genetically modified rKRKTNF under the conditions described in the text was approximately 55%. The biological activity of liposomal rKRKTNF, as tested with an in vitro cytotoxicity assay was reduced compared to the free, unconjugated rKRKTNF. In vivo biodistribution studies showed that conjugation of as little as 0. 13% of the grafted PEG chains resulted in a rapid elimination of the formulation from the blood stream. It is speculated that both non-selective conjugate chemistry and inherent recognition of the TNF by the components of the reticuloendothelial system (RES) are responsible for the short blood half life of the rKRKTNF-PEG-liposomes. The result suggest that conjugating a rapidly clearing recombinant cytokine to long-circulating liposomes provides little advantage in modifying the pharmacokinetic parameters of the cytokine.

Animals↗
PubMed2005

[Strategies for safety assessment of genetically modified crops: current and future development].

Gene recombinant technologies supply agriculture product with great vitality. But the risk of genetically modified crops cannot be ignored. The international organizations such as WHO, FAO and OECD have reached common agreement: the safety of transgenic crops should be thoroughly evaluated based on "substantial equivalence"principle. The relevant strategies including: substantial equivalent analysis, toxic tests, protein allergenic study, nutritional assessment, etc. With the development of new technologies, the approaches of genomic, proteomics, metabolomics would be applied to detect the unintended effects. The EU recently adopted legislation on the cultivation GM crops requiring the post market surveillance for any unanticipated adverse effects in the long term. In conclusion, the strategies of the safety assessment of GM crop are very strict and likely development.

Animals↗
PubMed2005

Detection of genetically modified organisms in foreign-made processed foods containing corn and potato.

Investigations of the validity of labeling regarding genetically modified (GM) products were conducted using polymerase chain reaction (PCR) methods for foreign-made processed foods made from corn and potato purchased in the Tokyo area and in the USA. Several kinds of GM crops were detected in 12 of 32 samples of processed corn samples. More than two GM events for which safety reviews have been completed in Japan were simultaneously detected in 10 samples. GM events MON810 and Bt11 were most frequently detected in the samples by qualitative PCR methods. MON810 was detected in 11 of the 12 samples, and Bt11 was detected in 6 of the 12 samples. In addition, Roundup Ready soy was detected in one of the 12 samples. On the other hand, CBH351, for which the safety assessment was withdrawn in Japan, was not detected in any of the 12 samples. A trial quantitative analysis was performed on six of the GM maize qualitatively positive samples. The estimated amounts of GM maize in these samples ranged from 0.2 to 2.8%, except for one sample, which contained 24.1%. For this sample, the total amount found by event-specific quantitative analysis was 23.8%. Additionally, Roundup Ready soy was detected in one sample of 21 potato-processed foods, although GM potatoes were not detected in any sample.

DNA, Plant↗
PubMed2003

Bypassing antibiotic selection: positive screening of genetically modified cells with an antigen-dependent proliferation switch.

While antibiotic selection has been routinely used for the selection of genetically modified cells, administration of cytotoxic drugs often leads to deleterious effects not only to inert cells but also to transfected or transduced ones. In this study, we propose an Antigen-MEdiated Genetically modified cell Amplification (AMEGA) system employing antibody/receptor chimeras without antibiotic selection. Based on a rational design where the extracellular domains of dimeric erythropoietin receptor (EpoR) or gp130 were substituted with heterodimeric V(H)/V(L) regions of anti-hen egg lysozyme (HEL) antibody and EpoR D2 domains, the genes encoding the chimeras as well as a model transgene, enhanced green fluorescent protein (EGFP), were retrovirally infected into IL-3-dependent Ba/F3 cells followed by direct HEL selection in the absence of IL-3. After a single round of selection, EGFP-positive cells were selectively amplified, resulting in a population of almost 100% positive cells. The AMEGA without antibiotic selection will not harm normal cells, which will be especially useful for increasing the efficacy for stem cell-based gene therapy.

Animals↗
PubMed2006

A microarray-based detection system for genetically modified (GM) food ingredients.

A multiplex DNA microarray chip was developed for simultaneous identification of nine genetically modified organisms (GMOs), five plant species and three GMO screening elements, i.e. the 35S promoter, the nos terminator and the nptII gene. The chips also include several controls, such as that for the possible presence of CaMV. The on-chip detection was performed directly with PCR amplified products. Particular emphasis was placed on the reduction of the number of PCR reactions required and on the number of primers present per amplification tube. The targets were biotin labelled and the arrays were detected using a colorimetric methodology. Specificity was provided by specific capture probes designed for each GMO and for the common screening elements. The sensitivity of the assay was tested by experiments carried out in five different laboratories. The limit of detection was lower than 0.3% GMO for all tests and in general around 0.1% for most GMOs. The chip detection system complies with the requirements of current EU regulations and other countries where thresholds are established for the labelling of GMO.

Agrobacterium tumefaciens↗
PubMed2006

Review: Genetically modified plants for the promotion of human health.

Plants are attractive biological resources because of their ability to produce a huge variety of chemical compounds, and the familiarity of production in even the most rural settings. Genetic engineering gives plants additional characteristics and value for cultivation and post-harvest. Genetically modified (GM) plants of the "first generation" were conferred with traits beneficial to producers, whereas GM plants in subsequent "generations" are intended to provide beneficial traits for consumers. Golden Rice is a promising example of a GM plant in the second generation, and has overcome a number of obstacles for practical use. Furthermore, consumer-acceptable plants with health-promoting properties that are genetically modified using native genes are being developed. The emerging technology of metabolomics will also support the commercial realization of GM plants by providing comprehensive analyzes of plant biochemical components.

Carotenoids↗
PubMed2005

Unpacking atitudes towards genetically modified food.

The present study investigates the structure of attitudes towards genetically modified (GM) food. A total of 431 respondents completed a questionnaire measuring their overall attitude, cognition and affect towards GM food. A model with distinct positive and negative, affective and cognitive components and a separate factor for perceived risk and worry best accounted for the data. Negative--but not positive--components directly affected behavioural intentions. Implications of these findings for our understanding of attitudes towards GM food and their impact on behaviour are discussed.

Adult↗
PubMed2004

Preferences need no inferences, once again: germinal elements in the public perceptions of genetically modified foods in Colombia.

This paper explores the public perceptions of genetically modified foods in Colombia in a phase considered germinal: the topic was too novel at the time of research. The analysis covers media, informal conversations, and the word associations made by a sample of residents in the city of Bogotá. The results show that the public capability of associating with the topic, even intuitively, is due to the availability of culture themes, the primary categories that help conceptual elaborations, and the construction of common-sense theories. Three themes are proposed: natural/artificial, tradition/change, and health/disease. It is argued that cultural themes are not only cognitive, but also affectively laden entities, which explains the evaluative force expressed by social beliefs. Acknowledging the relevance of the non-attitude thesis, the author suggests that people associate novel objects with latent cultural meanings, explaining why words, images, and metaphors are readily available in elaborating social knowledge.

Colombia↗
PubMed2003

A novel approach to the use of genetically modified herbicide tolerant crops for environmental benefit.

The proposed introduction of genetically modified herbicide tolerant (GMHT) crops, with claims of improved weed control, has prompted fears about possible environmental impacts of their widespread adoption, particularly on arable weeds, insects and associated farmland birds. In response to this, we have developed a novel weed-management system for GMHT sugar beet, based on band spraying, which exploits the flexibility offered by the broad-spectrum partner herbicides. Here, we show the results from two series of field experiments which, taken together, demonstrate that, by using this system, crops can be managed for enhanced weed and insect biomass without compromising yield, thus potentially offering food and shelter to farmland birds and other wildlife. These results could be applicable widely to other row crops, and indicate that creative use of GMHT technology could be a powerful tool for developing more sustainable farming systems in the future.

Animals↗
PubMedDate not supplied

Assessing the allergenicity of proteins introduced into genetically modified crops using specific human IgE assays.

Global commercial production of genetically modified (GM) crops has grown to over 67 million hectares annually, primarily of herbicide-tolerant and insect protection crop varieties. GM crops are produced by the insertion of specific genes that either encode a protein, or a regulatory RNA sequence. A comprehensive safety evaluation is conducted for each new commercial GM crop, including an assessment of the potential allergenicity of any newly introduced protein. If the gene was derived from an allergenic organism, or the protein sequence is highly similar to a known allergen, immunoassays, e.g., Western blot assays and enzyme-linked immunosorbent assay tests, are performed to identify protein-specific IgE binding by sera of individuals allergic to the gene source, or the source of the sequence-matched allergen. Although such assays are commonly used to identify previously unknown allergens, criteria have not been established to demonstrate that a protein is unlikely to cause allergic reactions. This review discusses factors that affect the predictive value of these tests, including clinical selection criteria for serum donors, selection of blocking reagents to reduce nonspecific antibody binding, inhibition assays to verify specificity of binding, and scientifically justified limits of detection (sensitivity) in the absence of information regarding biological thresholds.

Allergens↗
PubMed2005

Nanoparticle-based DNA biosensor for visual detection of genetically modified organisms.

Although screening of raw ingredients and food products for genetically modified organisms (GMO) may be accomplished by detecting either the exogenous DNA or the novel protein, DNA is the preferred analyte because of its superior stability during food processing. The development of DNA biosensors is of increasing importance due to the growing demand for rapid and reliable methods for GMO detection. We report the first DNA biosensor in a dry-reagent dipstick configuration for visual detection and confirmation of GMO-related sequences by hybridization within minutes. The sensor is disposable and does not require special instrumentation. It detects the 35S promoter and nopaline synthase (NOS) terminator sequences that are present in the majority of transgenic plants. The target sequences are amplified by the polymerase chain reaction (PCR) and hybridized (7min) with probes bearing oligo(dA) tail. The biotinylated product is applied to the sensor followed by immersion in the appropriate buffer. Migration of the buffer rehydrates gold nanoparticles conjugated to oligo(dT), which hybridize with the oligo(dA) tails. The hybrids are captured by immobilized streptavidin at the test zone of the sensor giving a characteristic red line due to the accumulation of the nanoparticles. The excess of nanoparticle conjugates are captured at the control zone by immobilized oligo(dA) strands. Amplified 35S or NOS DNA is detectable at 0.16nM. Soybean powder certified reference material with 0.1% GMO content is clearly detectable after 35 and 40 amplification cycles for 35S and NOS sequence, respectively. The sensor was also applied to real samples from various sources.

Biosensing Techniques↗
PubMed2002

Degradation of transgenic DNA from genetically modified soya and maize in human intestinal simulations.

The inclusion of genetically modified (GM) foods in the human diet has caused considerable debate. There is concern that the transfer of plant-derived transgenes to the resident intestinal microflora could have safety implications. For these gene transfer events to occur, the nucleic acid would need to survive passage through the gastrointestinal tract. The aim of the present study was to evaluate the rate at which transgenes, contained within GM soya and maize, are degraded in gastric and small bowel simulations. The data showed that 80 % of the transgene in naked GM soya DNA was degraded in the gastric simulations, while no degradation of the transgenes contained within GM soya and maize were observed in these acidic conditions. In the small intestinal simulations, transgenes in naked soya DNA were degraded at a similar rate to the material in the soya protein. After incubation for 30 min, the transgenes remaining in soya protein and naked DNA were 52 (sem 13.1) % and 34 (sem 17.5) %, respectively, and at the completion of the experiment (3 h) these values were 5 % and 3 %, respectively. In contrast to the soya transgene, the maize nucleic acid was hydrolysed in the small intestinal simulations in a biphasic process in which approximately 85 % was rapidly degraded, while the rest of the DNA was cleaved at a rate similar to that in the soya material. Guar gum and tannic acid, molecules that are known to inhibit digestive enzymes, did not influence the rate of transgene degradation in soya protein. In contrast guar gum reduced the rate of transgene degradation in naked soya DNA in the initial stages, but the polysaccharide did not influence the amount of nucleic acid remaining at the end of the experiment. Tannic acid reduced the rate of DNA degradation throughout the small bowel simulations, with 21 (sem 5.4) % and 2 (sem 1.8) % of the naked soya DNA remaining in the presence and absence of the phenolic acid, respectively. These data indicate that some transgenes in GM foods may survive passage through the small intestine.

DNA, Plant↗