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Regulatory issues for genetically modified animals

Perry Bradbury HACKETT

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 188-203 doi: 10.15302/J-FASE-2019307

摘要:

Precision genetics and breeding have the potential to meet the agricultural needs and goals of the world in the 21st century. These needs include increasing the efficiency of production of animals and improving their products with minimal impact on the environment. The USA is the major innovator in genomic science and the acknowledged leader in formulating policies to regulate genetic applications in medicine and agriculture. However, governments worldwide have been exceedingly reluctant to support the introduction of genetically modified (GM) animals into agriculture. Regulatory policies have stagnated due to legal guidelines that could not anticipate the needs and solutions that are evident today. This must change if we are to maintain planetary integrity. I propose a new, market-based regulatory model for GM livestock that has both a strong scientific foundation and has worked for 10000 years. The model is similar to that for information technology in which specific algorithms drive computer and cell phone applications. Genome engineers write genetic algorithms that drive the traits in biological organisms. Accordingly, GM products should be viewed in terms of their use and public benefit rather than by limitations to the genetic programing coming from a few highly vocal groups. Genetic algorithms (Genapps) of the 21st century will include not only introduction of synthetic genes, but also complete natural and synthetic biochemical pathways to produce agricultural products that are maximally efficient, healthy to humans and animals, and sustainable in an era of changing climates while avoiding environmental degradation.

关键词: algorithms     editing     FDA     GMO     recombinant DNA     USDA    

High-expression of recombinant human concensus interferon-α by Pichia pastoris

HAO Yuyou, SHI Qiqi, HE Yun, ZHUANG Yingping, WANG Yonghong, ZHANG Siliang, CHU Ju, LIU Zhimin

《化学科学与工程前沿(英文)》 2007年 第1卷 第4期   页码 399-403 doi: 10.1007/s11705-007-0073-x

摘要: The present work focused on the high expression of recombinant human consensus interferon- (cIFN) by Pichia pastoris. The cycle of glycerol feeding, the strategy of methanol feeding and the optimum pH for protein induction were studied. The optimized strategies were a 4-h glycerol-feeding period, induction pH being kept at 5.0 and methanol concentration being kept under 5 g/L. The maximum dry cell weight, cIFN production and bioactivity obtained were 168, 1.24 g/L and 5.4×10 U/mL, respectively.

关键词: bioactivity     pastoris     maximum     induction     optimized    

Expression and function of DMT1 without IRE in C6 cells mediated by recombinant adenovirus

Xixun DU*, Huamin XU*, Hong JIANG, Jun WANG, Lei WANG, Junxia XIE

《医学前沿(英文)》 2009年 第3卷 第1期   页码 67-71 doi: 10.1007/s11684-009-0010-0

摘要: Divalent metal transporter 1 (DMT1) is a ferrous iron import protein. The improper expression of DMT1 is involved in neurodegenerative diseases. In the present study, we constructed a recombinant adenovirus containing the gene of DMT1 without the iron response element (DMT1-IRE) and investigated its expression and function in the C6 glioma cell line. The DMT1-IRE gene, obtained by RT-PCR, was cloned into the shuttle plasmid pAdTrack-CMV containing green fluorescent protein (GFP) reporter gene. Linearized plasmid pAdTrack-CMV-DMT1-IRE was subsequently co-transformed into ( ) BJ5183 cells along with an adenoviral backbone plasmid pAdEasy-1 after digestion with I. I-digested pAdEasy1-DMT1-IRE was then transfected into E1-transformed human embryonic kidney cells (HEK293 cells) , in which recombinant adenoviruses were generated within 7 to 10 days. The results demonstrated that we obtained the DMT1-IRE gene. pAdEasy1-DMT1-IRE yielded a large fragment, plus a smaller fragment of 4.5 kb after digestion with I. PCR confirmed pAdEasy1-DMT1-IRE contained gene DMT1-IRE, indicating the successful construction of recombinant adenovirus plasmid containing DMT1-IRE. GFP fluorescence further confirmed the generation of adenovirus. AdDMT1-IRE could efficiently infect C6 glioma cells. And cell viability decreased in Ad-DMT1-IRE infected cells after iron overload compared to the control. These results suggest that the over expressed DMT1-IRE can aggravate the iron induced cell death due to its iron influx function.

关键词: divalent metal transporter 1     recombinant adenovirus     homologous recombination     iron    

Construction of a universal recombinant expression vector that regulates the expression of human lysozyme

Shen LIU, Shengzhe SHANG, Xuezhen YANG, Huihua ZHANG, Dan LU, Ning LI

《农业科学与工程前沿(英文)》 2018年 第5卷 第3期   页码 382-389 doi: 10.15302/J-FASE-2018211

摘要:

The mammary gland provides a novel method for producing recombinant proteins in milk of transgenic animals. A key component in the technology is the construction of an efficient milk expression vector. Here, we established a simple method to construct a milk expression vector, by a combination of homologous recombination and digestion-ligation. Our methodology is expected to have the advantages of both plasmid and bacterial artificial chromosome (BAC) vectors. The BAC of mouse whey acidic protein gene (mWAP) was modified twice by homologous recombination to produce a universal expression vector, and the human lysozyme gene (hLZ) was then inserted into the vector by a digestion-ligation method. The final vector containing the 8.5 kb mWAP 5′ promoter, 4.8 kb hLZ genomic DNA, and 8.0 kb mWAP 3′ genomic DNA was microinjected into pronuclei of fertilized mouse embryos, to successfully generate two transgenic mouse lines that expressed recombinant human lysozyme (rhLZ) in milk. The highest expression level of rhLZ was 0.45 g·L1, and rhLZ exhibited the same antibacterial activity as native hLZ. Our results have provided a simple approach to construct a universal milk expression vector, and demonstrated that the resulting vector regulates the expression of hLZ in milk.

关键词: BAC recombinant methods     gene expression     human lysozyme     transgenic mice     milk expression vector    

Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing

《医学前沿(英文)》 2022年 第16卷 第6期   页码 919-931 doi: 10.1007/s11684-021-0918-6

摘要: Preeclampsia (PE) is characterized by placenta-mediated pregnancy complication. The only effective treatment for PE is the delivery of the placenta. However, this treatment may cause preterm birth and neonatal death. Therefore, preventing PE is needed. The mechanism of PE involves abnormal placentation, which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation. These mediators contribute to systemic vascular dysfunction, inflammatory responses, and excessive thrombin generation. Microparticles (MPs) are reportedly involved in PE by promoting the thromboinflammatory response. This study describes a strategy to prevent PE by reducing MP release using the recombinant protein, diannexin. Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation. Additionally, diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells. Moreover, in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice. Furthermore, diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro. These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.

关键词: preeclampsia     recombinant protein diannexin     microparticle     NLRP3 inflammasome     phosphatidylserin    

工程化DNA材料构建DNA活字系统实现可持续的数据存储 Article

巩子祎, 宋理富, 裴广胜, 董雨菲, 李炳志, 元英进

《工程(英文)》 2023年 第29卷 第10期   页码 130-136 doi: 10.1016/j.eng.2022.05.023

摘要:

DNA分子作为一种具有潜力的数据存储绿色材料,具有密度高和保存期长的优势。然而,目前DNA数据存储的数据写入依赖于DNA从头合成,写入成本高昂,且产生有害物,限制了其实际应用。在本研究中,我们开发了一种DNA活字存储系统,该系统可以利用由细胞工厂预生产的DNA活字片段进行数据写入。在这个系统中,这些预先生成的DNA片段,在这里称为“DNA活字”,是可重复使用的基本数据单元。通过这些DNA活字的快速组装来实现数据写入,从而避免了昂贵且对环境有害的DNA化学合成过程。通过DNA活字片段的反复使用和生物组装,该系统在降低写入成本方面的潜力非常突出,为经济和可持续的DNA数据存储技术开辟了一条新颖路线。

关键词: 合成生物学     DNA信息存储     DNA活字存储系统     经济性DNA数据存储    

Clinical evaluation of recombinant human growth hormone injection in children with growth hormone deficiency

Ling HOU, Xiaoping LUO, Minlian DU, Huamei MA, Chunxiu GONG, Yuchuan LI, Shuixian SHEN, Zhuhui ZHAO, Li LIANG, Guanping DONG, Chaoying YAN, Hongwei DU

《医学前沿(英文)》 2009年 第3卷 第2期   页码 171-176 doi: 10.1007/s11684-009-0027-4

摘要: Recombinant human growth hormone (rhGH) has been widely used in the clinical treatment of growth hormone deficiency. To simplify the injection process and increase drug compliance, application of the GH injection has become a new treatment plan in recent years. The purpose of the current study was to evaluate the efficacy and safety of rhGH injection for the treatment of growth hormone deficiency (GHD) in children in China. In a nationwide, noncomparative, prospective, randomized, open trial, 31 children with confirmed complete GHD received subcutaneous injection of rhGH at 0.25 mg/kg·wk (0.107 IU/kg·d). The injection was given daily and the total weekly amount was separated into 6-7 injections. The patients were followed up at 3-month intervals and the treatment duration was 12 months. The height (HT), annual growth velocity (GV), mean height standard deviation score (HT SDS), blood serum insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and bone maturity before and after treatment were compared, and the safety of the treatment was analyzed. The mean HT, GV, and HT SDS were increased from 109.0±14 cm, 2.7±0.9 cm/yr, and -4.62±1.46 at baseline to 121.8±13.4 cm, 12.9±3.3 cm/yr, and -2.47±1.86 after 12 months of treatment, respectively ( <0.001). At the same time, blood IGF-I and IGFBP-3 were increased significantly [41.27±64.43 μg/L 159.21±167.92 μg/L and 1540.00±1325.11 mg/L 3533.93±1413.82 mg/L, respectively ( <0.001)]. The bone age assessments performed 6 and 12 months after the treatment showed that no advanced bone maturation was noted. No serious adverse events occurred during the treatment, and the drug-related adverse events were mainly decreased thyroid function. We conclude that rhGH injection is a safe and effective drug for treatment of growth hormone deficiency in children.

关键词: recombinant human growth hormone     injection     growth hormone deficiency    

supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant

Wei Wang, Shuqin Jiang, Zhirui Cui, Xiangyang Luo, Lingli Shi, Heli Zheng

《医学前沿(英文)》 2018年 第12卷 第5期   页码 580-585 doi: 10.1007/s11684-017-0585-9

摘要:

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5–3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.

关键词: therapeutic     idiopathic short-stature children     free T4     the first year     recombinant human growth hormone    

The role of PARP1 in the DNA damage response and its application in tumor therapy

null

《医学前沿(英文)》 2012年 第6卷 第2期   页码 156-164 doi: 10.1007/s11684-012-0197-3

摘要:

Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.

关键词: PARP1     synthetic lethality     PARP inhibitor     DNA repair     cancer     NHEJ    

Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

《化学科学与工程前沿(英文)》 2011年 第5卷 第2期   页码 179-187 doi: 10.1007/s11705-009-0268-4

摘要: Ataxia-telangiectasia mutated (ATM) plays a key role in regulating the cellular response to ionizing radiation. The tumor-suppressor gene ATM, mutations in which cause the human genetic disease ataxia telangiectasia, encodes a key protein kinase that controls the cellular response to double-stranded breaks. Activation of ATM results in phosphorylation of many downstream targets that modulate numerous damage response pathways, most notably cell cycle checkpoints. Here, we highlight some of the new developments in the field in our understanding of the mechanism of activation of ATM and its signaling pathways, explore whether DNA double-strand breaks are the sole activators of ATM and ATM-dependent signaling pathways, and address some of the prominent, unanswered questions related to ATM and its function. The scope of this article is to provide a brief overview of the recent literature on this subject and to raise questions that could be addressed in future studies.

关键词: ataxia-telangiectasia mutated (ATM)     cell cycle checkpoint     DNA damage     signalling transduction    

Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

《医学前沿(英文)》 2014年 第8卷 第2期   页码 201-216 doi: 10.1007/s11684-014-0324-4

摘要:

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

关键词: class switch recombination     somatic hypermutation     activation-induced deaminase     DNA repair     genomic instability    

Molecular simulation of the interaction mechanism between CodY protein and DNA in

Linchen Yuan, Hao Wu, Yue Zhao, Xiaoyu Qin, Yanni Li

《化学科学与工程前沿(英文)》 2019年 第13卷 第1期   页码 133-139 doi: 10.1007/s11705-018-1737-4

摘要: In , the global transcriptional regulatory factor CodY can interact with the promoter DNA to regulate the growth, metabolism, environmental adaptation and other biological activities of the strains. In order to study the mechanism of interaction between CodY and its target DNA, molecular docking and molecular dynamics simulations were used to explore the binding process at molecular level. Through the calculations of the free energy of binding, hydrogen bonding and energy decomposition, nine key residues of CodY were identified, corresponding to SER184, SER186, SER208, THR217, ARG218, SER219, ASN223, LYS242 and GLY243, among which SER186, ARG218 and LYS242 play a vital role in DNA binding. Our research results provide important theoretical guidance for using wet-lab methods to study and optimize the metabolic network regulated by CodY.

关键词: CodY     DNA     molecular docking     molecular dynamics    

Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

《医学前沿(英文)》 2015年 第9卷 第3期   页码 261-274 doi: 10.1007/s11684-015-0406-y

摘要:

Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

关键词: environmental pollution     DNA methylation     cancer     biomarker     diagnosis     therapy     prevention    

Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

《农业科学与工程前沿(英文)》 2014年 第1卷 第3期   页码 185-190 doi: 10.15302/J-FASE-2014035

摘要: DNA damage is one of the most common threats to meiotic cells. It has the potential to induce infertility and genetic abnormalities that may be passed to the embryo. Here, we reviewed exogenous factors which could induce DNA damage. Specially, we addressed the different effects of DNA damage on mouse oocytes and embryonic development. Complex DNA damage, double-strand breaks, represents a more difficult repair process and involves various repair pathways. Understanding the mechanisms involved in DNA damage responses may improve therapeutic strategies for ovarian cancer and fertility preservation.

关键词: DNA damage     double-strand breaks (DSBs)     oocyte     embryo    

表征不同DNA高阶结构的单分子分析方法 Review

刘泳麟, 边天元, 刘岩, 李治民, 裴羽丰, 宋杰

《工程(英文)》 2023年 第24卷 第5期   页码 277-292 doi: 10.1016/j.eng.2022.10.009

摘要:

DNA不仅是生命遗传信息的载体,而且是一种高度可编程和自组装的纳米材料。不同的DNA结构与其生物学和化学功能有关。因此,了解各种DNA结构的物理和化学性质在生物学和纳米化学中具有重要意义。然而,群体分子实验忽略了溶液中DNA结构的异质性。单分子分析方法是观察单个分子的行为和探测自由能态的高异质性的有力工具。本文介绍了单分子检测和操纵等单分子分析方法,并讨论了这些方法如何用于测量单/双链DNA(ss/dsDNA)、DNA高阶结构和DNA纳米结构的分子性质。最后,将DNA纳米技术和单分子分析方法进行结合以了解DNA和其他生物物质、软物质的生物物理特性。

关键词: 单分子分析方法     DNA结构     力学性能     构象转变    

标题 作者 时间 类型 操作

Regulatory issues for genetically modified animals

Perry Bradbury HACKETT

期刊论文

High-expression of recombinant human concensus interferon-α by Pichia pastoris

HAO Yuyou, SHI Qiqi, HE Yun, ZHUANG Yingping, WANG Yonghong, ZHANG Siliang, CHU Ju, LIU Zhimin

期刊论文

Expression and function of DMT1 without IRE in C6 cells mediated by recombinant adenovirus

Xixun DU*, Huamin XU*, Hong JIANG, Jun WANG, Lei WANG, Junxia XIE

期刊论文

Construction of a universal recombinant expression vector that regulates the expression of human lysozyme

Shen LIU, Shengzhe SHANG, Xuezhen YANG, Huihua ZHANG, Dan LU, Ning LI

期刊论文

Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing

期刊论文

工程化DNA材料构建DNA活字系统实现可持续的数据存储

巩子祎, 宋理富, 裴广胜, 董雨菲, 李炳志, 元英进

期刊论文

Clinical evaluation of recombinant human growth hormone injection in children with growth hormone deficiency

Ling HOU, Xiaoping LUO, Minlian DU, Huamei MA, Chunxiu GONG, Yuchuan LI, Shuixian SHEN, Zhuhui ZHAO, Li LIANG, Guanping DONG, Chaoying YAN, Hongwei DU

期刊论文

supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant

Wei Wang, Shuqin Jiang, Zhirui Cui, Xiangyang Luo, Lingli Shi, Heli Zheng

期刊论文

The role of PARP1 in the DNA damage response and its application in tumor therapy

null

期刊论文

Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

期刊论文

Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

期刊论文

Molecular simulation of the interaction mechanism between CodY protein and DNA in

Linchen Yuan, Hao Wu, Yue Zhao, Xiaoyu Qin, Yanni Li

期刊论文

Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

期刊论文

Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

期刊论文

表征不同DNA高阶结构的单分子分析方法

刘泳麟, 边天元, 刘岩, 李治民, 裴羽丰, 宋杰

期刊论文