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PubMed2006

Genetically modified pigs produced with a nonviral episomal vector.

Genetic modification of cells and animals is an invaluable tool for biotechnology and biomedicine. Currently, integrating vectors are used for this purpose. These vectors, however, may lead to insertional mutagenesis and variable transgene expression and can undergo silencing. Scaffold/matrix attachment region-based vectors are nonviral expression systems that replicate autonomously in mammalian cells, thereby making possible safe and reliable genetic modification of higher eukaryotic cells and organisms. In this study, genetically modified pig fetuses were produced with the scaffold/matrix attachment region-based vector pEPI, delivered to embryos by the sperm-mediated gene transfer method. The pEPI vector was detected in 12 of 18 fetuses in the different tissues analyzed and was shown to be retained as an episome. The reporter gene encoded by the pEPI vector was expressed in 9 of 12 genetically modified fetuses. In positive animals, all tissues analyzed expressed the reporter gene; moreover in these tissues, the positive cells were on the average 79%. The high percentage of EGFP-expressing cells and the absence of mosaicism have important implications for biotechnological and biomedical applications. These results are an important step forward in animal transgenesis and can provide the basis for the future development of germ-line gene therapy.

Animals↗
PubMed2003

Risks and benefits of genetically modified maize donations to southern Africa: views from Malawi.

In 2001 and 2002, many countries in the Southern African Development Community (SADC) have suffered from severe food shortages resulting in an estimated 14 million people facing starvation due to inadequate quantities of the staple maize. The international community's response has been the donation of foodstuffs, including genetically modified maize. Reactions of the recipient countries of Zambia, Zimbabwe, and Malawi have been different. Zambia appealed to the donors not to send genetically modified maize, whereas Malawi accepted the maize donations. Malawi is currently facing many public health challenges because 10% of its 10-million population is HIV-positive, maternal mortality rate has almost doubled between 1992 and 2000, and there are also an estimated 1 million orphans due to HIV/AIDS. In the European Union, genetically modified maize falls under "Novel Foods" and its marketing and distribution are strictly regulated by law. This has never been the case in the southern African countries. In this article, we discuss the ethical challenges associated with genetically modified maize donations to southern Africa. Although genetically modified food offers a way to avoid many adverse effects of food shortages, we believe that some of the ethical questions of genetically modified food donations should be solved first, under the leadership of the donor countries and partnership of the developing countries. There are fears that consummation of genetically modified maize could have adverse health effects. These fears must be addressed if the confidence of developing countries in the donor community is to be maintained.

Bioethical Issues↗
PubMed2003

Model studies on the detectability of genetically modified feeds in milk.

Detecting the use of genetically modified feeds in milk has become important, because the voluntary labeling of milk and dairy products as "GMO free" or as "organically grown" prohibits the employment of genetically modified organisms (GMOs). The aim of this work was to investigate whether a DNA transfer from foodstuffs like soya and maize was analytically detectable in cow's milk after digestion and transportation via the bloodstream of dairy cows and, thus, whether milk could report for the employment of transgene feeds. Blood, milk, urine, and feces of dairy cows were examined, and foreign DNA was detected by polymerase chain reaction by specifically amplifying a 226-bp fragment of the maize invertase gene and a 118-bp fragment of the soya lectin gene. An intravenous application of purified plant DNA showed a fast elimination of marker DNA in blood or its reduction below the detection limit. With feeding experiments, it could be demonstrated that a specific DNA transfer from feeds into milk was not detectable. Therefore, foreign DNA in milk cannot serve as an indicator for the employment of transgene feeds unless milk is directly contaminated with feed components or airborne feed particles.

Animal Feed↗
PubMed1994

Genetically modified skin to treat disease: potential and limitations.

Molecular definition of disease at the level of the gene and advances in recombinant DNA technology suggest that many diseases are amenable to correction by genes not bearing the defective elements that result in disease. Many questions must be answered before this therapy can be used to correct chronic diseases. These questions fall into safety and efficacy categories. Experience with transplanting cellular elements of skin or skin substitutes (defined as skin that possess the cell types and a dermal structure to develop into a functioning skin) to athymic rodents is considerable and is seen as a system where these questions can be answered. This paper reviews these questions and presents our early analysis of genetically modified cells in skin substitutes in vivo and in vitro. Experimental data demonstrate that both a matrix of woven nylon, housing a fibroblast generated collage, and dead dermis can be utilized to shuttle genetically modified human fibroblasts from the laboratory to an in vivo setting. Genetically modified fibroblasts do not migrate from the shuttle to the surrounding tissue. The survival of significant numbers, approximately 70%, of genetically modified fibroblasts for at least 6 weeks in these shuttles, supports this general approach as having clinical utility. It is also concluded that skin substitute systems can be used to generate a genetically modified skin in vitro that has the capacity to develop into functional skin in vivo. Further, as genetically modified keratinocytes differentiate there is increased production by the transgene, supporting the concept that keratinocytes have true potential as shuttles for therapeutic genes. This work demonstrates that transplantation of systems containing genetically modified cells of the skin can be used to experimentally define many aspects of gene therapy using skin before this technology is taken to the clinic. Examples include determining the effect of gene transduction and expression on structure and function of the genetically modified skin as well as on distant skin and an assessment of the translational capacity of the transgene as function of time and cell number.

3T3 Cells↗
PubMed2003

[Monitoring of food products from genetically modified sources in Moscow].

This paper presents results of a detection of genetically modified organisms (GMO) in food from the shops of Moscow. The screening methods and event-specific assay based on the polymerase chain reaction is used. Transgenic DNA from genetically modified soybeans line 40-3-2 is detected in 17.2% samples of studied foods. Soybeans line 40-3-2 is allowed in Russian food supply.

Food Analysis↗
PubMed1997

Use of cloned genetically modified human fibroblasts to assess long-term survival in vivo.

Because human fibroblasts are easily brought to tissue culture conditions and can be stably transduced with retroviral vectors encoding transgenes ex vivo, genetically modified fibroblasts are frequently considered in strategies to correct disease with gene therapy. This enthusiasm has been dampened by studies showing that transgene expression by genetically modified fibroblasts diminishes with time in vivo, but not in vitro, for reasons that are unclear. We elected to study this problem using cloned human fibroblasts that had been cloned by limiting dilution and stably transduced with a retroviral vector encoding lacZ ex vivo. These were seeded onto a nonbiodegradable nylon matrix that was transplanted to nude mice. Transgene expression was followed prospectively by histologic exam. Data show that human fibroblasts can withstand the pressure of cloning by limiting dilution. In addition, they can be passaged from 10 to > 20 times, and > 1 x 10(20) of genetically modified fibroblasts can be generated as progeny of one cell. Loss of transgene expression by the cloned genetically modified fibroblasts in vivo occurs in an orderly and progressive fashion, but is not complete by 4 months. Neither the loss nor the persistence of expression appear to be random. These observations are most compatible with the thesis that a major cause of the loss of transgene expression in vivo is secondary to apoptosis of the genetically modified fibroblast. Loss of expression of transgenes in senescent genetically modified fibroblasts occurs more rapidly than in their presenescent counterparts in the age-neutral, in vivo setting of the nude mouse.

Animals↗
PubMed2005

Perceived naturalness and acceptance of genetically modified food.

This study examines people's acceptance of genetically modified (GM) food. Results suggest that GM acceptance depends most on how natural the genetically modified product is perceived and not directly on how natural the non-GM product is seen. A GM product that is perceived as more natural is more likely to be accepted than a GM product that is perceived as less natural. The extent to which GM affects the perceived naturalness of a product partly depends on the kind of product.

Adolescent↗
PubMed2001

Use of cloned DNA fragments as reference materials for event specific quantification of genetically modified organisms (GMOs).

For the quantification of genetically modified organisms (GMOs) in foods and feeds, real-time PCR is currently the most widely applied technique. To obtain a % of GMO, a GMO-specific target sequence is quantified relatively to a species-specific sequence. The correctness and reliability of the obtained quantitative results fully depend on the reference materials used as standards for setting up external calibration curves. We introduced a completely new type of standards for quantification of GMOs, based on cloned plasmid DNA solutions with well-known amounts of the sequences of interest, expressed as copy numbers. Moreover, the junction sequence between inserted DNA and plant DNA was used as 'unique identifier'. In this study, the model was applied for Roundup Ready soybean.

Calibration↗
PubMed2004

Effects of feeding rations with genetically modified whole cottonseed to lactating Holstein cows.

Two experiments were conducted to evaluate dry matter intake (DMI), milk yield, and milk composition from feeding rations that contained different sources of genetically modified whole cottonseed to Argentinean Holstein dairy cows. Twenty-four lactating multiparous Argentinean Holstein dairy cows were used in 2 experiments with a replicated 4 x 4 Latin square design, with cows averaging 565 kg body weight and 53 d in milk at the beginning of the experiments. Treatments in Experiment 1 were: Bollgard cotton containing the cry1Ac gene, Bollgard II cotton containing cry1Ac and cry2Ab genes, Roundup Ready cotton containing the cp4 epsps gene, and a control nongenetically modified but genetically similar cottonseed. In Experiment 2, two commercial sources, a parental control line, and the transgenic cotton containing both cry1Ac and cp4 epsps genes were used as treatments. All cows received the same total mixed ration but with different whole cottonseed sources. Cottonseed was included to provide 2.50 kg per cow daily (dry matter [DM] basis) or about 10% of the total diet DM. The ingredient composition of the total mixed ration was 32% alfalfa hay, 28% corn silage, 22% corn grain, 17% soybean meal, and 2% minerals and vitamins. In addition, genomic DNA was extracted from a subset of milk samples and analyzed by polymerase chain reaction followed by Southern blot hybridization for small fragments of the cry1Ac transgene and an endogenous cotton gene, acp1. No sample was positive for transgenic or plant DNA fragments at the limits of detection for the assays following detailed data evaluation criteria. The DMI, milk yield, milk composition, body weight, and body condition score did not differ among treatments. Cottonseed from genetically modified varieties used in these studies yielded similar performance in lactating dairy cows when compared to non-transgenic control and reference cottonseed.

Animal Feed↗
PubMed2002

Genetically modified foods: a taste of the future.

Technologies for genetically modifying foods hold tremendous promise for meeting important public health challenges in this century. By keeping informed of the ongoing development of genetically modified foods, nurses can effectively educate patients about the benefits and risks of these foods and promote informed decision making.

Food Technology↗
PubMed2000

Safety assessment of rice genetically modified with soybean glycinin by feeding studies on rats.

Feeding studies on rice genetically modified with soybean glycinin were performed on rats for four weeks. The rats were divided into three groups, each being fed on (I) only a commercial diet, (II) this diet plus control rice and (III) this diet plus rice genetically modified with glycinin. The rats were fed with 10 g/kg-weight of rice every day by oral administration. During the test period, the rats in every group grew well without marked differences in appearance, food intake, body weight, or cumulative body weight gain. There were also no significant differences in the blood count, blood composition or internal organ weights among the rats. Necropsy at the end of the experiment indicated neither pathological symptoms nor histopathological abnormalities in the liver and kidney. Judging from these results, the rice genetically modified with glycinin is considered to have been essentially the same in nutritional and biochemical characteristics as the control rice.

Animal Feed↗
PubMedDate not supplied

[Accuracy of a real-time polymerase-chain-reaction assay for a quantitative estimation of genetically modified sources in food products].

The accuracy of a real-time polymerase-chain-reaction assay for genetically modified sources in food products was determined using two official test systems (kits) of primers and samples. These kits were recommended by the Federal Center of State Sanitary and Epidemiological Surveillance (Russian Ministry of Health) and the European Commission. We used the following three models of thermocyclers: iCycler iQ (BioRad, United States), Rotor-Gene 3000 (Corbett Research, Australia), and DT-322 (DNA-Technology, Russia). Studies of samples that contained 1% genetically modified sources showed that the error of a quantitative assay for genetically modified sources in food products corresponds to 20-30% and does not depend on the kit type and the thermocycler model used.

DNA Primers↗
PubMed2004

Explaining public resistance to genetically modified corn: an analysis of the distribution of benefits and risks.

Genetically modified (GM) crops have met with widespread approval among scientists and policy makers in the United States, but public approval of GM crops, both domestically and abroad, is progressing much more slowly. An underlying cause of public wariness may be that both nations and individual consumers do not perceive significant benefits to themselves from GM crops, while fearing the risks they may incur. In this study, an economic analysis is conducted to determine whether the benefits of one type of GM corn, Bt corn (genetically modified to resist damage from the ECB and Southwestern corn borer), outweigh the potential risks; and who the "winners" and "losers" are among stakeholder groups that may be affected by Bt corn. It is found that Bt corn growers, consumers, and industry all benefit from Bt corn adoption, though the purported health and environmental benefits of reducing chemical pesticide usage through Bt corn are negligible. Though the aggregated public benefit is large, the welfare gain to individual consumers is small and may not make up for perceived risks. While environmental and health risks of Bt corn are unlikely, the potential market risks-impacting both the organic corn market and total U.S. corn exports-are found to be significant. Currently, distributional analysis is not a part of regulatory decision making of Bt corn in the United States; yet it may help to explain why decision makers at both the government and individual-consumer levels have failed to embrace Bt corn and other GM crops.

Food, Genetically Modified↗
PubMed2005

Competitive engraftment of hematopoietic stem cells genetically modified with a truncated erythropoietin receptor.

Transplantation of genetically modified hematopoietic stem cells (HSCs) has therapeutic potential for a variety of blood genetic disorders. Engraftment of HSCs, however, requires toxic myeloablative treatments, which render this approach questionable for non-life-threatening disorders. A potential alternative is the use of transgenes, which allows positive selection of HSCs in vivo. We used retroviral vectors to express a truncated derivative of the erythropoietin receptor (tEpoR) in murine and human hematopoietic cells. Murine HSCs expressing tEpoR at different levels (1500 to 13,000 receptors/cell) acquire a competitive repopulation capacity in vivo upon transplantation into fully or partially myeloablated co-isogenic mouse recipients. Long-term analysis of transplanted mice showed that expression of tEpoR at paraphysiological levels (approximately 1500 receptors/cell) has no effect on steady-state hematopoiesis and induces no further expansion of transduced cells after the engraftment period. Human cord blood-derived CD34+ stem/progenitor cells transduced with a lentiviral vector expressing tEpoR expand their clonogenic capacity in vitro, and significantly increase their marrow repopulation capacity upon xenotransplantation into sublethally irradiated NOD-SCID mice, with no alteration in their phenotype, survival, and differentiation properties. These data indicate that expression of tEpoR is an effective strategy to promote selective engraftment of genetically modified HSCs upon transplantation in both myeloablative and nonmyeloablative conditions, without the use of toxic drugs for selection.

Animals↗
PubMed2005

Event specific qualitative and quantitative polymerase chain reaction detection of genetically modified MON863 maize based on the 5'-transgene integration sequence.

Because of the genetically modified organisms (GMOs) labeling policies issued in many countries and areas, polymerase chain reaction (PCR) methods were developed for the execution of GMO labeling policies, such as screening, gene specific, construct specific, and event specific PCR detection methods, which have become a mainstay of GMOs detection. The event specific PCR detection method is the primary trend in GMOs detection because of its high specificity based on the flanking sequence of the exogenous integrant. This genetically modified maize, MON863, contains a Cry3Bb1 coding sequence that produces a protein with enhanced insecticidal activity against the coleopteran pest, corn rootworm. In this study, the 5'-integration junction sequence between the host plant DNA and the integrated gene construct of the genetically modified maize MON863 was revealed by means of thermal asymmetric interlaced-PCR, and the specific PCR primers and TaqMan probe were designed based upon the revealed 5'-integration junction sequence; the conventional qualitative PCR and quantitative TaqMan real-time PCR detection methods employing these primers and probes were successfully developed. In conventional qualitative PCR assay, the limit of detection (LOD) was 0.1% for MON863 in 100 ng of maize genomic DNA for one reaction. In the quantitative TaqMan real-time PCR assay, the LOD and the limit of quantification were eight and 80 haploid genome copies, respectively. In addition, three mixed maize samples with known MON863 contents were detected using the established real-time PCR systems, and the ideal results indicated that the established event specific real-time PCR detection systems were reliable, sensitive, and accurate.

Animals↗
PubMed2001

Assessment of the food safety issues related to genetically modified foods.

International consensus has been reached on the principles regarding evaluation of the food safety of genetically modified plants. The concept of substantial equivalence has been developed as part of a safety evaluation framework, based on the idea that existing foods can serve as a basis for comparing the properties of genetically modified foods with the appropriate counterpart. Application of the concept is not a safety assessment per se, but helps to identify similarities and differences between the existing food and the new product, which are then subject to further toxicological investigation. Substantial equivalence is a starting point in the safety evaluation, rather than an endpoint of the assessment. Consensus on practical application of the principle should be further elaborated. Experiences with the safety testing of newly inserted proteins and of whole genetically modified foods are reviewed, and limitations of current test methodologies are discussed. The development and validation of new profiling methods such as DNA microarray technology, proteomics, and metabolomics for the identification and characterization of unintended effects, which may occur as a result of the genetic modification, is recommended. The assessment of the allergenicity of newly inserted proteins and of marker genes is discussed. An issue that will gain importance in the near future is that of post-marketing surveillance of the foods derived from genetically modified crops. It is concluded, among others that, that application of the principle of substantial equivalence has proven adequate, and that no alternative adequate safety assessment strategies are available.

Genetic Engineering↗
PubMed2006

Development of an innovative immunoassay for CP4EPSPS and Cry1AB genetically modified protein detection and quantification.

An innovative immunoassay, called enzyme-linked immunoabsorbant assay (ELISA) Reverse, based on a new conformation of the solid phase, was developed. The solid support was expressly designed to be immersed directly in liquid samples to detect the presence of protein targets. Its application is proposed in those cases where a large number of samples have to be screened simultaneously or when the simultaneous detection of different proteins is required. As a first application, a quantitative immunoassay for Cry1AB protein in genetically modified maize was optimized. The method was tested using genetically modified organism concentrations from 0.1 to 2.0%. The limit of detection and limit of quantitation of the method were determined as 0.0056 and 0.0168 (expressed as the percentage of genetically modified organisms content), respectively. A qualitative multiplex assay to assess the presence of two genetically modified proteins simultaneously was also established for the case of the Cry1AB and the CP4EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) present in genetically modified maize and soy, respectively.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMedDate not supplied

In vivo and in vitro degradation of urea and uric acid by encapsulated genetically modified microorganisms.

This study was undertaken to characterize the capacity of a combination of genetically modified bacteria to lower elevated levels of urea and uric acid and thus to serve as a potential adjunct to maintenance dialysis in patients with chronic renal failure. Two strains of genetically modified bacteria expressing enzymes, urease to degrade urea and uricase to degrade uric acid, were identified, combined, and dispersed in 600-microm alginate microcapsules suitable for oral administration. In 24 h in vitro experiments, 5 mL of these capsules completely cleared 95% of the urea and >99% of the uric acid from 100 mL of a challenge solution formulated to the concentration of these solutes in a presenting hemodialysis patient. The process of urea degradation was found to be intracellular and each bacterial strain was specific for its substrate. Solute degradation in vivo was evaluated with a chemically induced model of acute renal failure, using Sprague-Dawley rats. Orally administered capsules were found to remain in the gastrointestinal tract for at least 6 h. The severity of azotemia and hyperuricaemia after chemical induction of acute renal failure was reduced by 64 and 31%, respectively, on administration of the capsules. Reduction of urea concentration (but not uric acid concentration) in vivo required coadministration of an ion-exchange resin to adsorb ammonia. Oral delivery of a combination of genetically modified microorganisms should be further explored in chronic renal failure models as a useful adjunct to dialysis or to immunosorption for the treatment of uremia.

Acute Kidney Injury↗