期刊文献+
共找到14篇文章
< 1 >
每页显示 20 50 100
Generation of knockout rabbits using transcription activator-like effector nucleases 被引量:1
1
作者 Yu Wang Nana Fan +10 位作者 Jun Song Juan Zhong Xiaogang Guo Weihua Tian Quanjun Zhang Fenggong Cui Li Li Philip N Newsome Jon Frampton Miguel A Esteban Liangxue Lai 《Cell Regeneration》 2014年第1期21-29,共9页
Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platformscontributing to redefine the boundaries of modern biological research. They are composed of a non-specificcleav... Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platformscontributing to redefine the boundaries of modern biological research. They are composed of a non-specificcleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications byinducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases havebeen employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, respectively.This approach is cost effective, relatively quick, and can produce invaluable models for human disease studies,biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbitsusing transcription activator-like effector nucleases, and a perspective of the field. 展开更多
关键词 RABBITS Animal models Zinc-finger nucleases transcription activator-like effector nucleases taleNs Genome editing KNOCKOUT
原文传递
类转录激活因子效应物核酸酶(TALEN)介导的基因组定点修饰技术 被引量:52
2
作者 沈延 肖安 +3 位作者 黄鹏 王唯晔 朱作言 张博 《遗传》 CAS CSCD 北大核心 2013年第4期395-409,共15页
人工构建的序列特异性核酸内切酶能够识别并切割特定的DNA靶序列,造成双链断裂,从而引起基因组结构的定点改变。人工核酸内切酶技术使得研究人员有可能对任意物种的基因组进行定点修饰,开启了反向遗传学研究的新天地。类转录激活因子效... 人工构建的序列特异性核酸内切酶能够识别并切割特定的DNA靶序列,造成双链断裂,从而引起基因组结构的定点改变。人工核酸内切酶技术使得研究人员有可能对任意物种的基因组进行定点修饰,开启了反向遗传学研究的新天地。类转录激活因子效应物核酸酶(Transcription activator-like effector nuclease,TALEN)自2010年底开始成功应用于基因打靶,很快成为一种比锌指核酸酶(Zinc-finger nuclease,ZFN)更容易设计、特异性更高和毒性更低的人工核酸内切酶。文章综述了TALEN技术的研究进展及应用前景,重点介绍TALEN的结构、作用机制与构建方法和利用TALEN进行基因组定点修饰的策略,以及目前利用这一技术已成功实现突变的物种及内源基因,特别是在斑马鱼中的应用,为开展这一领域的研究工作提供参考。 展开更多
关键词 类转录激活因子效应物(tale) 类转录激活因子效应物核酸酶(taleN) 人工核酸内切酶(EEN) 基因组编辑 基因组定点修饰
下载PDF
Highly efficient generation of GGTA1 knockout pigs using a combination of TALEN m RNA and magnetic beads with somatic cell nuclear transfer 被引量:7
3
作者 FENG Chong LI Xi-rui +5 位作者 CUI Hui-ting LONG Chuan LIU Xia TIAN Xing-hua PAN Deng-ke LUO Yu-zhu 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2016年第7期1540-1549,共10页
The transcription activator-like effector nuclease (TALEN) technique combined with the somatic cel nuclear transfer (SCNT) method has been successfuly applied for creating geneticaly modiifed pigs. However, method... The transcription activator-like effector nuclease (TALEN) technique combined with the somatic cel nuclear transfer (SCNT) method has been successfuly applied for creating geneticaly modiifed pigs. However, methods for isolating cels with bialelic indels requires further improvement because of the relatively low enrichment efifciency of mutated somatic cels. Moreover, little is known regarding the off-target effects of the TALEN system and the heredity of TALEN-modiifed pigs. In this study, an efifcient method to increase the enrichment efifciency of TALEN-mediated bialelic knockout (KO) cels was established, and corresponding geneticaly modiifed pigs with the expected genotype were generated whose off-target effect, fertility and heredity characteristics were aslo evaluated. Two TALEN pairs were constructed to target the porcine α-1,3-galactosyltransferase (GGTA1) gene locus. TALEN mRNA was transfected into the ear ifbroblasts folowed by the enrichment of α-Gal nul cels of minipigs using isolectin B4 (IB4) lectin and magnetic beads. A total of 115 cel colonies were formed and validated to beGGTA1 KO cels by sequencing and 10 bialelic KO cel colonies were used as nuclear donors for SCNT. ThirtyGGTA1 bialelic KO piglets were successfuly delivered and grew normaly. Seventeen potential off-target sites were investigated, and no off-target events were detected in the live piglets. To determine the fertility and heredity characteristics of TALEN-modiifed pigs, 10 mature founders were mated with each other and the mutations were determined to be transmitted to the F1 piglets. We established a robust and safe technology for developing geneticaly modiifed pig lines with expected genotypes for agricultural breeding and biomedical application. 展开更多
关键词 transcription activator-like effector nuclease taleN) magnetic beads somatic cel nuclear transfer (SCNT) off-target geneticaly modiifed pigs
下载PDF
The key residues of OsTFIIAγ5/Xa5 protein captured by the argininerich TFB domain of TALEs compromising rice susceptibility and bacterial pathogenicity 被引量:2
4
作者 TIAN Jing-jing HUI Shu-gang +1 位作者 SHI Ya-rui YUAN Meng 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2019年第6期1178-1188,共11页
Xanthomonas bacteria secrete transcription activator-like effector(TALE)proteins into host cells to activate plant disease susceptibility genes to cause disease,and the process is dependent on interaction between bact... Xanthomonas bacteria secrete transcription activator-like effector(TALE)proteins into host cells to activate plant disease susceptibility genes to cause disease,and the process is dependent on interaction between bacteria TFB domain of TALEs and host plant basal transcription factor IIA gamma subunit(TFIIAγ).The key domain or residues of plant TFIIAγand core residues of bacteria TFB domain that are indispensable for TFIIAγ-TALEs interaction in the process of TALE-carrying Xanthomonas invasion plants are unknown.Here,we showed that the thirdα-helix domain of OsTFIIAγ5/Xa5,especially the 38th,39th,40th and 42th residues were key sites for capturing by TALEs of Xanthomonas oryzae pv.oryzae(Xoo),the causal agent of rice bacterial blight disease.The latter segment of Xoo TFB domain harboring seventy-two amino acid residues was vital for TALE specific binding with host plant OsTFIIAγ5/Xa5.Substitution of some residues in this core region of TFB domain completely compromised capacity of TALEs capturing rice OsTFIIAγ5/Xa5.The rich and conserved arginine residues in this core region of TFB domain were responsible for TALE-dependent plant susceptibility gene activation and virulence of Xoo.These results provide a potential strategy for improving resistance to TALE-carrying pathogens in plants by site-specific modification of key residues of host plant TFIIAγ. 展开更多
关键词 XANTHOMONAS transcription activator-like effector PthXo1 TFB RICE
下载PDF
TALE靶标基因与农作物广谱持久抗病育种
5
作者 徐夏萌 徐正银 +3 位作者 李颖 阎依超 邹丽芳 陈功友 《上海交通大学学报》 EI CAS CSCD 北大核心 2021年第S01期36-38,共3页
为了揭示黄单胞菌与植物间互作的遗传学基础,培育广谱持久抗病的农作物,本文对这一领域重要研究进展进行了综述.首先指出了黄单胞菌引起植物病害的严重性,分析了黄单胞菌与植物互作如何导致植物抗病或感病,归纳了TALE蛋白主要作用植物... 为了揭示黄单胞菌与植物间互作的遗传学基础,培育广谱持久抗病的农作物,本文对这一领域重要研究进展进行了综述.首先指出了黄单胞菌引起植物病害的严重性,分析了黄单胞菌与植物互作如何导致植物抗病或感病,归纳了TALE蛋白主要作用植物的靶标类型,分析了植物基础转录因子TFIIA与NLR类R基因在植物抗病性中的重要性,认为基因编辑TALE蛋白的效应子结合元件(EBE)是未来作物广谱持久抗病育种的重要方向. 展开更多
关键词 黄单胞菌 tale 抗病基因 感病基因 抗病育种
下载PDF
Regulation of IL12B Expression in Human Macrophages by TALEN-mediated Epigenome Editing
6
作者 Meng CHEN Hua ZHU +6 位作者 Yu-juan MAO Nan CAO Ya-li YU Lian-yun LI Qiu ZHAO Min WU Mei YE 《Current Medical Science》 SCIE CAS 2020年第5期900-909,共10页
Although the exact etiology of inflammatory bowel disease(IBD)remains unclear,exaggerated immune response in genetically predisposed individuals has been reported.Th1 and Th17 cells mediate IBD development.Macrophages... Although the exact etiology of inflammatory bowel disease(IBD)remains unclear,exaggerated immune response in genetically predisposed individuals has been reported.Th1 and Th17 cells mediate IBD development.Macrophages produce IL-12 and IL-23 that share p40 subunit encoded by IL12B gene as heteromer partner to drive Th1 and Th17 differentiation.The available animal and human data strongly support the pathogenic role of IL-12/IL-23 in IBD development and suggest that blocking p40 might be the potential strategy for IBD treatment.Furthermore,aberrant alteration of some cytokines expression via epigenetic mechanisms is involved in pathogenesis o f IBD.In this study,we analyzed core promoter region of IL12B gene and investigated whether IL12B expression could be regulated through targeted epigenetic modification with gene editing technology.Transcription activator-like effectors(TALEs)are widely used in the field of genome editing and can specifically target DNA sequence in the host genome.We synthesized the TALE DNA-binding domains that target the promoter of human IL12B gene and fused it with the functional catalytic domains of epigenetic enzymes.Transient expression of these engineered enzymes demonstrated that the TALE-DNMT3A targeted the selected IL12B promoter region,induced loci-specific DNA methylation,and down-regulated IL-12B expression in various human cell lines.Collectively,our data suggested that epigenetic editing of IL12B through methylating DNA on its promoter might be developed as a potential therapeutic strategy for IBD treatment. 展开更多
关键词 transcription activator-like effectors epigenome editing DNA methylation CYTOKINE IL12B inflammatory bowel disease
下载PDF
rAL Effectors Drive Transcription Bidirectionally in Plants 被引量:2
7
作者 Li Wang Fabio C. Rinaldi +6 位作者 Pallavi Singh Erin L. Doyle Zoe E. Dubrow Tuan Tu Tran Alvaro L. Perez-Quintero Boris Szurek Adam J. Bogdanove 《Molecular Plant》 SCIE CAS CSCD 2017年第2期285-296,共12页
TAL effectors delivered by phytopathogenic Xanthomonas species are DNA-sequence-specific transcrip- tional activators of host susceptibility genes and sometimes resistance genes. The modularity of DNA recognition by T... TAL effectors delivered by phytopathogenic Xanthomonas species are DNA-sequence-specific transcrip- tional activators of host susceptibility genes and sometimes resistance genes. The modularity of DNA recognition by TAL effectors makes them important also as tools for gene targeting and genome editing. Effector binding elements (EBEs) recognized by native TAL effectors in plants have been identified only on the forward strand of target promoters. Here, we demonstrate that TAL effectors can drive plant tran- scription from EBEs on either strand and in both directions. Furthermore, we show that a native TAL effector from Xanthomonas oryzae pv. oryzicola drives expression of a target with an EBE on each strand of its promoter. By inserting that promoter and derivatives between two reporter genes oriented head to head, we show that the TAL effector drives expression from either EBE in the respective orientations, and that activity at the reverse-strand EBE also potentiates forward transcription driven by activity at the forward-strand EBE. Our results reveal new modes of action for TAL effectors, suggesting the possibility of yet unrecognized targets important in plant disease, expanding the search space for off-targets of custom TAL effectors, and highlighting the potential of TAL effectors for probing fundamental aspects of plant transcription. 展开更多
关键词 XANTHOMONAS transcription activator-like effector bidirectional reporter enhancer element off-target
原文传递
类转录激活因子效应物及其在生物技术领域的应用 被引量:1
8
作者 吴伦英 景晓辉 沈雁 《热带生物学报》 2013年第4期386-392,共7页
综述了类转录激活因子效应物(TALEs)技术的研究进展及生物技术应用前景,重点介绍TALEs的结构特征、作用机理、广谱抗性基因的人工构建及利用类转录激活因子效应物核酸酶(Transcription activator like effector nucleases,TALENs)进行... 综述了类转录激活因子效应物(TALEs)技术的研究进展及生物技术应用前景,重点介绍TALEs的结构特征、作用机理、广谱抗性基因的人工构建及利用类转录激活因子效应物核酸酶(Transcription activator like effector nucleases,TALENs)进行基因组定点修饰的策略。 展开更多
关键词 类转录激活因子效应物 类转录激活因子效应物核酸酶 结构特征 生物技术应用前景
下载PDF
自发光转录激活子样效应因子的功能分析
9
作者 吴云华 杨盼春 李勇 《中南民族大学学报(自然科学版)》 CAS 2018年第3期23-27,共5页
目的:对转录激活子样效应因子(TALE)蛋白进行特异性标记.方法:通过分子生物学技术,在TALE蛋白的C-端融合了一种具有优异光学性能的萤光素酶.结果:融合蛋白不仅可对目的 DNA进行特异性识别,还可产生萤光素酶的特征光谱.结论:萤光素酶的... 目的:对转录激活子样效应因子(TALE)蛋白进行特异性标记.方法:通过分子生物学技术,在TALE蛋白的C-端融合了一种具有优异光学性能的萤光素酶.结果:融合蛋白不仅可对目的 DNA进行特异性识别,还可产生萤光素酶的特征光谱.结论:萤光素酶的融合不影响TALE蛋白的正常功能,其光谱信息有望成为分析TALE蛋白与DNA相互作用的特异性检测信号. 展开更多
关键词 转录激活子样效应因子蛋白 重组蛋白质 蛋白质表达与纯化 生物发光 萤光素酶
下载PDF
Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease 被引量:11
10
作者 Isaac G. Onyango 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第1期19-25,共7页
Alzheimer’s disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved... Alzheimer’s disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria. 展开更多
关键词 Alzheimer's disease mitochondria BIOENERGETICS mitochondrial DNA neuroinflammation mitohormesis caloric restriction HYPOMETABOLISM MITOPHAGY mitochondrial biogenesis recombinant-human mitochondrial transcription factor A antioxidants PROTEASOME mitochondrial transcription activator-like effector nucleases clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) caloric restriction stem cells
下载PDF
Cautious optimism in anticipation of hepatitis B curative therapies
11
作者 Alla Turshudzhyan Micheal Tadros 《World Journal of Virology》 2022年第4期212-215,共4页
Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or c... Despite relative effectiveness of current hepatitis B therapies,there is still no curative agents available.The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen.Studies or clinical trials investigating new therapies remain small and either focus on patients with low viral load and without hepatotoxic injury or patients with hepatitis D co-infection,which makes it challenging to assess their effectiveness and side effect profile in hepatitis B population. 展开更多
关键词 Hepatitis B Hepatitis B virus Hepatitis B virus entry inhibitor Bulevirtide transcription activator-like effector nucleases Zinc-finger nucleases Clustered regularly interspaced short palindromic repeats-associated 9 Nucleocapsid assembly modulators Hepatitis B virus transcription inhibitors Hepatitis B surface antigen release inhibitors
下载PDF
碱基编辑系统的研究进展 被引量:1
12
作者 钟静丽 林健香 +1 位作者 周建奎 乔云波 《生物工程学报》 CAS CSCD 北大核心 2024年第5期1271-1292,共22页
基于可编程核酸酶的基因编辑工具表现出编辑高效、产物纯度高、编辑副产物少的优势,已广泛应用于生物医药研发和作物育种。鉴于研究和应用的需求多样化,开发功能特异的碱基编辑器成为基因编辑领域的研究热点。目前由规律成簇的间隔短回... 基于可编程核酸酶的基因编辑工具表现出编辑高效、产物纯度高、编辑副产物少的优势,已广泛应用于生物医药研发和作物育种。鉴于研究和应用的需求多样化,开发功能特异的碱基编辑器成为基因编辑领域的研究热点。目前由规律成簇的间隔短回文重复序列系统及相关蛋白(clustered regularly interspaced short palindromic repeats and CRISPR-associated, CRISPR-Cas)和转录激活因子类效应因子(transcription activator-like effector, TALE)系统衍生的基因编辑系统包括单碱基编辑器、双碱基编辑器、线粒体碱基编辑器和CRISPR相关转座酶系统等。本文全面梳理了碱基编辑系统的发展历程,总结了各类碱基编辑器的特点、脱靶效应、优化和改良策略等,为基因编辑系统的进一步改进和应用提供参考。 展开更多
关键词 规律成簇的间隔短回文重复序列系统及相关蛋白9(CRISPR-Cas9) 碱基编辑器 转录激活因子类效应因子(tale)系统 脱氨酶
原文传递
The genetic arms race between plant and Xanthomonas:lessons learned from TALE biology 被引量:1
13
作者 Jiao Xue Zhanhua Lu +4 位作者 Wei Liu Shiguang Wang Dongbai Lu Xiaofei Wang Xiuying He 《Science China(Life Sciences)》 SCIE CAS CSCD 2021年第1期51-65,共15页
The pathogenic bacterial genus Xanthomonas infects a wide variety of host plants and causes devastating diseases in many crops.Transcription activator-like effectors(TALEs)are important virulence factors secreted by X... The pathogenic bacterial genus Xanthomonas infects a wide variety of host plants and causes devastating diseases in many crops.Transcription activator-like effectors(TALEs)are important virulence factors secreted by Xanthomonas with the ability to directly bind to the promoters of target genes in plant hosts and activate their expression,which often facilitates the proliferation of pathogens.Understanding how plants cope with TALEs will provide mechanistic insights into crop breeding for Xanthomonas defense.Over the past 30 years,numerous studies have revealed the modes of action of TALEs in plant cells and plant defense strategies to overcome TALE attack.Based on these findings,new technologies were adopted for disease management to optimize crop production.In this article,we will review the most recent advances in the evolutionary arms race between plant resistance and TALEs from Xanthomonas,with a specific focus on TALE applications in the development of novel breeding strategies for durable and broad-spectrum resistance. 展开更多
关键词 transcription activator-like effectors XANTHOMONAS susceptibility genes resistance genes tale application
原文传递
新型靶向基因组编辑技术研究进展 被引量:6
14
作者 杨发誉 葛香连 谷峰 《中国生物工程杂志》 CAS CSCD 北大核心 2014年第2期98-103,共6页
传统的靶向基因组编辑技术改造基因效率非常低,严重制约了基础研究和临床应用。因此,新的靶向基因组编辑工具的研究显得非常重要,以此来提高基因原位修复、定点整合及高通量基因敲除的效率。主要论述了近年来发现的新型靶向基因组编辑... 传统的靶向基因组编辑技术改造基因效率非常低,严重制约了基础研究和临床应用。因此,新的靶向基因组编辑工具的研究显得非常重要,以此来提高基因原位修复、定点整合及高通量基因敲除的效率。主要论述了近年来发现的新型靶向基因组编辑技术即锌指核酸酶(ZFN)、转录激活子样效应因子核酸酶(TALENs)、规律成簇间隔短回文重复(CRISPR)/Cas系统。从它们的发现、结构和研究进展及应用前景等方面进行了总结;通过比较三者的优缺点,发现规律成簇间隔短回文重复(CRISPRs)具有明显的优点。 展开更多
关键词 靶向基因编辑 锌指核酸酶(ZFN) 转录激活子样效应因子核酸酶(taleNs) 规律成簇间隔短回文重复(CRISPRs) Zinc Finger nucleases(ZFN) transcription activator-like effector NUCLEASES (taleNs) Clustered regularly interspaced short palindromic repeats(CRISPRs)
原文传递
上一页 1 下一页 到第
使用帮助 返回顶部