Safety Assessment of Genetically Modified Foods

The development of novel foods produced through agricultural biotechnology is a complex three-stage process: gene discovery, line selection, and product advancement to commercialization. The safety of genetically modified foods is an integral part of the overall developmental process throughout all of the stages. In the discovery stage, the safety of the gene, its source, and the gene products must be considered. If any questions arise at this stage, these questions must be answered later in the developmental process. During the line selection stage, the genetically modified seed progresses through a variety of greenhouse and field trials. At this stage, the biological and agronomic equivalence of the genetically modified crop to its traditional counterpart must be compared. While the evaluations made during this stage are not specifically directed toward a safety assessment, many potential products with unusual characteristics are eliminated during this stage of development. However, the elimination of products with unusual agronomic or biological characteristics enhances the likelihood that a safe product will be generated. Finally, in the pre-commercialization stage, the genetically modified product undergoes a detailed safety assessment process. This process focuses on the safety of the gene products associated with the introduced gene and any other likely toxicological or anti-nutrient factors associated with the source of the novel gene and the crop to which it was introduced. The safety of the genetically modified product for both food and feed uses is considered. Thus far, all of the genetically modified products brought into the marketplace have been subjected to such an intensive safety assessment. The safety assessment data have been reviewed by regulatory authorities around the world. The current generation of genetically modified products are quite safe for human and feed animal consumption.     

理性认识转基因植物食品的安全性

讨论现代生物技术的几个基本概念 ,如转基因生物、基因修饰生物、重组DNA植物以及对转基因植物食品安全性评价框架 ,阐明作者对转基因植物食品安全性的理解。     

A 90-Day Feeding Study in Rats to Assess the Safety of Genetically Engineered Pork

Our laboratory recently produced genetically engineered (GE) Meishan pigs containing a ZFN-edited myostatin loss-of-function mutant. These GE pigs develop and grow as normal as wild type pigs but produce pork with greater lean yield and lower fat mass. To assess any potential subchronic toxicity risks of this GE pork, a 90-day feeding study was conducted in Sprague-Dawley rats. Rats were randomly divided into five groups, and fed for 90 days with basic diet and basic diets formulated with low dose and high dose pork prepared from wild type pigs and GE pigs, respectively. Animal behaviors and clinical signs were monitored twice daily, and body weight and food consumption were measured and recorded weekly. At days 45 and 90, blood tests (lipid panel, electrolytes, parameters related to liver and kidney functions, and complete blood counts) were performed. Additionally, gross pathology and histopathological analyses were performed for major organs in each group. Data analysis shows that there were no significant differences in growth rate, food consumption, and blood test parameters between rat groups fed with GE pork and wild type pork. Although differences in some liver function parameters (such as aspartate aminotransferase, total proteins, albumin, and alkaline phosphatase) and white blood cell counts (such as lymphocyte percentage and monocyte percentage) were observed between rats fed with high dose GE pork and basic diet, all test results in rats fed with GE pork are in the normal range. Additionally, there are no apparent lesions noted in all organs isolated from rats in all five feeding groups on days 45 and 90. Overall, our results clearly indicate that food consumption of GE pork produced by ZFN-edited myostatin loss-of-function mutant pigs did not have any long-term adverse effects on the health status in rats.     

Genetically Engineered Animal Models of Alzheimer's Disease

The application of transgenic research has proven to be a powerful and popular tool for investigating the contribution of specific genes known or suspected to be involved in the pathology of Alzheimer's disease. Many different experimental approaches have been pursued in an effort to mimic one or more of the numerous and diverse features characterizing Alzheimer's disease. Results have been variable but not without successes. Some of the cardinal hallmarks of this disorder have been recapitulated through the manipulation of a single gene, providing information on the interrelationship between several pathological events. Also, through the generation of such transgenic animals, potential models are being established for this disease that will be valuable for development of intervention strategies.     

制备遗传工程小鼠的技术改进

遗传工程小鼠是当今生命科学领域集成度最高的研究体系之一。特别在“人类基因组计划和小鼠基因组计划”完成后,遗传工程小鼠在制备人类疾病模型、药物开发和评价、基因功能分析以及比较基因组学中发挥着越来越重要的作用。由此,也推动了遗传工程小鼠相关技术的快速发展。就遗传工程小鼠制备的现况、存在的问题以及新策略等相关问题进行了总结。     

基因工程抗体融合蛋白的构建

抗体融合蛋白可以具有抗体的特性和所融合的功能蛋白的活性,可广泛用于免疫治疗、免疫诊断、抗体纯化及抗体和抗原的分析定量等,特别可用于免疫导向药物的制备。基因工程抗体融合蛋白比传统的化学交联的抗体融合蛋白具有更多的优越性。本文就基因工程抗体融合蛋白的构建和性质做一综述 。     

转基因植物的生态风险

转基因植物已在很多国家大规模商业化种植,并且取得了显著的经济效益。同时有关转基因植物潜在的生态风险已引起广泛的关注。本文从转基因植物人侵危害、对非靶标有益生物直接和间接的影响、害虫对抗虫转基因植物产生抗性、抗病毒转基因植物带来的潜在风险等方面论述了转基因植物可能潜在的生态安全性问题。     

基因工程菌在生物降解中的应用及其发展

在简要阐述基因工程菌构建方法的基础上,系统综述和评价了基因工程构建方法的研究进展及其在生物降解中存在的问题。     

基因工程抗体研究进展

临床治疗中人抗鼠抗体反应的出现使鼠源性单克隆抗体的应用受到了极大的限制。为降低其免疫原性,人们利用基因工程技术对鼠源抗体进行改造,以减少其鼠源成分。简要概述了目前研究比较多的几种基因工程抗体及其临床应用。     

遗传工程微生物细胞间发生的自然遗传转化

将两株具有不同遗传标记的枯草芽孢杆菌在基本培养基中分别培养至对数生长后期后进行短时间混合静置培养,经选择平板筛选、DNaseI敏感性试验、质粒检测和产蛋白酶活性检测,发现两菌株之间可通过自然遗传转化进行染色体DNA和质粒DNA的交换。研究结果表明,自然遗传转化可在细胞间进行,这对揭示微生物群居的自然环境中可能存在的细胞间的DNA转移,以及正确评估遗传工程微生物(GEMs)的安全使用具有重要意义。 Abstract：The culture fluids of two genetically distinct Bacillus subtilis strains were mixed and coincubated for a short time after they reached post-exponentially growth phase in minimal media.The steadily bidirectional gene transfer involving chromosomal DNA and plasmid DNA by natural genetic transformation between these two strains has been demonstrated by the methods of selective medium screening,DNaseI sensitivity test,plasmid detection and the detection of the capability of producing protease.This result indicates that natural genetic transformation occurs not only between“naked”DNA and cells but also between cells.This conclusion is significant in the assessment of both the possibility of intercelluar DNA transfer in natural habitats of microorganisms and the risk of the application of genetically engineered microorganisms (GEMs).     

遗传工程微生物细胞间发生的自然遗传转化

将两株具有不同遗传标记的枯草芽孢杆菌在基本培养基中分别培养至对数生长后期后进行短时间混合静置培养 ,经选择平板筛选、DNaseI敏感性试验、质粒检测和产蛋白酶活性检测 ,发现两菌株之间可通过自然遗传转化进行染色体DNA和质粒DNA的交换。研究结果表明 ,自然遗传转化可在细胞间进行 ,这对揭示微生物群居的自然环境中可能存在的细胞间的DNA转移 ,以及正确评估遗传工程微生物(GEMs)的安全使用具有重要意义。     

Phytoremediation of Mercury- and Methylmercury-Polluted Soils Using Genetically Engineered Plants

Inorganic mercury in contaminated soils and sediments is relatively immobile, though biological and chemical processes can transform it to more toxic and bioavailable methylmercury. Methylmercury is neurotoxic to vertebrates and is biomagnified in animal tissues as it is passed from prey to predator. Traditional remediation strategies for mercury contaminated soils are expensive and site-destructive. As an alternative we propose the use of transgenic aquatic, salt marsh, and upland plants to remove available inorganic mercury and methylmercury from contaminated soils and sediments. Plants engineered with a modified bacterial mercuric reductase gene, merA, are capable of converting Hg(II) taken up by roots to the much less toxic Hg(0), which is volatilized from the plant. Plants engineered to express the bacterial organo-mercurial lyase gene, merB, are capable of converting methylmercury taken up by plant roots into sulfhydryl-bound Hg(II). Plants expressing both genes are capable of converting ionic mercury and methylmercury to volatile Hg(0) which is released into an enormous global atmospheric Hg(0) pool. To assess the phytoremediation capability of plants containing the merA gene, a variety of assays were carried out with the model plants Arabidopsis thaliana, and tobacco (Nicotiana tabacum).     

基于基因突变的基因工程抗体亲和力成熟研究

基因工程重组抗体可通过对基因序列的分析、修饰与修改,从而改进抗体特性。对基于基因突变的基因工程抗体亲和力成熟的方法进行总结,主要包括小分子有机物-抗体相互作用机制分析、抗体序列数据库及计算机模拟技术,以及新兴的分子模拟与对接技术。     

Bifurcation Analysis of Genetically Engineered Pacemaking in Mammalian Heart

Genetically engineered pacemaking in ventricular cells has been achieved by down-regulation of the time independent inward rectifying current (I _K1), or insertion of the hyperpolarisation-activated funny current (I _f). We analyse the membrane system (i.e. ionic concentrations clamped) of an epicardial Luo-Rudy dynamic cell model using continuation algorithms with the maximum conductance () of I _K1 and I _f as bifurcation parameters. Pacemaker activity can be induced either via Hopf or homoclinic bifurcations. As _K1 is decreased by ≈74%, autorhythmicity emerged via a homoclinic bifurcation, i.e., the periodicity first appear with infinitely large periods. In contrast, the insertion of _f induced periodicity via a subcritical Hopf bifurcation at _f≈ 0.25 mSμF⁻¹. Stable autorhythmic action potentials occurred at _f > 0.329 mSμF⁻¹.     

Genetically Engineered Human Cancer Models Utilizing Mammalian Transgene Expression

Cancer models are vital to cancer biology research, and multiple cancer models are currently available that utilize either murine or human cells, each with particular strengths and weaknesses. The ability to transform primary human cells into tumors through the expression of specific transgenes offers many advantages as a cancer model, including genetic malleability and the ability to transform specific cell types. Until recently, the conversion of primary human cells into tumors through transgene expression required the use of viral genetic elements, which unfortunately adds uncertainty regarding which cancer pathways are affected and how they are affected. In recent years multiple reports have described the transformation of primary human cells into tumors using only mammalian transgenes. This review focuses on these five cancer models, comparing the different cell types which were transformed into tumors and which transgenes were expressed, as well as the cancer pathways affected in the disparate models. These genetically-engineered human cancer models offer a valuable tool to complement existing cancer models and further cancer research.