四环素可调控基因表达系统的研究进展

近年来对人工合成可调控基因表达系统的研究较多,其中四环素调控表达系尤为突出,此系统已在基因功能研究、基因选择性表达分析方面得到了较好地应用。基因治疗是当前研究的热点之一,如何保证有效目的基因在体内适时、适量地表达是实现安全、有效的基因治疗的保障。因此,对此系统的改进及应用,将推动人类疾病基因治疗的进展     

Tet基因调控系统研究进展

Tet基因调控系统是将原核生物基因调控元件引入真核基因调控领域而构建的一种新型基因表达调控系统。它具有高效、无毒、严密的开 /关功能 ,故被广泛应用于基因表达调控、基因功能研究以及基因治疗中。     

严密型四环素调控系统转基因首建鼠的建立

目的制备ApoE-rtTA-tTS转基因小鼠1，为严密型四环素调控系统的体内研究提供调控部分的转基因小鼠，以便与反应部分小鼠交配得到双转基因小鼠。方法重组构建含目的基因的质粒pApoE-rtTA-tTS，应用显微注射法将其注入母鼠的受精卵，再植入代母输卵管，出生小鼠经PCR初步筛选出阳性，再经Southern杂交对阳性小鼠基因组DNA标本进一步鉴定。结果产生了2只整合ApoE-rtTA-tTS基因的首建鼠。结论成功制备了ApoE-rtTA-tTS转基因小鼠，为下一步建立严密型四环素调控系统的双转基因小鼠模型奠定了基础。     

四环素基因表达调控系统介导的HBV X基因体外表达细胞株的建立

目的：建立稳定，高效的HBxAg体外表达的细胞株，以便进一步研究HBV X基因和HBxAg的致癌作用及机理，方法：构建带有完整四环素基因关闭（Tet-off)系统的HBV X基因重组表达质粒pBPSTR1-FlagX，用该重组质粒转染NIH 3T3细胞，筛选嘌呤霉素抗性细胞克隆，用抗－FlagM2单抗和兔抗－HBx作蛋白质免疫印迹分析，检测细胞内Flag-HBxAg表达和四环素调控其表达的情况。结果：重组质粒pBPSTR1-FlagX转染NIH 3T3细胞后获得30个生长良好的嘌呤霉素抗性细胞克隆。其中12个细胞克隆有Flag-HBxAg的稳定表达，且有5个克隆的Flag-HBxAg表达受四环素调控，当四环素浓度逐渐增高时，细胞内Flag-HBxAg的表达逐渐减弱。四环素浓度达1μg/ml时，Flag-HBxAg表达被完全抑制。结论：本研究成功构建了四环素调控系统介导的HBV X基因体外表达细胞株，该细胞株不仅能稳定高水平地表达HBxAg，而且具有定时“开”“关”和定量调节HBxAg表达水平的特性，是HBVX基因功能研究的一个有用工具。     

New strategies in tetracycline-regulatable system

四环素基因调控系统(Tet系统)是迄今为止基因治疗研究中使用最广泛的系统,该系统通过改变培养基、体内四环素或其衍生物(如强力霉素)的浓度,诱导或抑制目标基因的表达.     

病毒性载体介导的基因转移研究进展

病毒性载体介导的基因转移研究进展迅残,并率先用于临床基因治疗试验。目前研究重点在对其进一步完善和发展,以及发现新的适于基因治疗的病毒性裁体,已获部分突破性进展,大大加速了基因治疗研究的进程,但也存在一些限制因素,尚需深入研究。     

基因治疗中的基因调控研究进展

基因治疗的目的是将导入的外源基因能够得到时序上、水平上的正确表达,其产物发挥治疗作用。目的基因表达的调控是影响基因治疗效果的一个重要因素。本文系统介绍了基因靶技术在基因治疗中的地位,提高逆转录病毒载体滴度的方法,逆转录病毒载体与目的基因序列的影响,反式激活提高目的基因应用以及对基因治疗中目的基因表达调控的展望。     

转移相关基因在肿瘤中的研究进展

 转移相关基因(metastasis-associated gene, MTA)是一个与肿瘤发生、进展和转移等密切相关的基因家族,其成员编码蛋白在多种人类肿瘤细胞中异常升高。最近的研究表明,转移相关基因可能是多种恶性肿瘤发生与进展相关的主要调节分子。本文针对目前转移相关基因在恶性肿瘤发生与进展过程中分子机制的研究及其在临床诊治中的应用做一综述。     

基因治疗新型病毒载体研究进展

基因转移载体是基因治疗能否进入临床应用的关键之一,本文就不断出现的新型病毒载体的研究方面的最新进展包括载体的构建、改造、表达调控和应用作了综述和评价。     

细胞凋亡的基因调控及应用展望

细胞凋亡的基因调控及应用展望１苏长青综述２龚西马俞审校作者单位：１南京八一医院电镜室，南京２１０００２２安徽医科大学病理学教研室，合肥２３００３２目前，虽然对细胞凋亡的激发与抑制的详细机制还不十分清楚，但已有许多研究资料证实，有多种基因参与了细胞凋亡...     

非病毒基因转运系统的研究进展

基因治疗已被视为人类最有希望彻底征服遗传性疾病和肿瘤等重大疾病的手段之一,发展非病毒基因转运系统对基因治疗的临床应用具有十分重要的推进作用。目前已发展了缓释系统介导的DNA体内转移,物理方法介导的基因转移及基于流体力学的基因转运系统。     

Therapeutic strategies for aberrant splicing in cancer and genetic disorders

Accurate pre-mRNA splicing is essential for proper protein translation; however, aberrant splicing is commonly observed in the context of cancer and genetic disorders. Notably, in genetic diseases, these splicing abnormalities often play a pivotal role. Substantial challenges persist in accurately identifying and classifying disease-induced aberrant splicing, as well as in development of targeted therapeutic strategies. In this review, we examine prevalent forms of aberrant splicing and explore potential therapeutic approaches aimed at addressing these splicing-related diseases. This summary contributes to a deeper understanding of the complexities about aberrant splicing and provide a foundation for the development of effective therapeutic interventions in the field of genetic disorders and cancer.     

中枢神经系统疾病的基因治疗

基因治疗正在成为常规方法难以治愈的中枢神经系统疾病的新的治疗手段。本文概要介绍了中枢神经系统疾病基因治疗的方法和途径；中枢神经系统疾病基因治疗的病毒载体以及目前中枢神经系统疾病基因治疗研究的状况。     

Neural stem cells and their role in recovery processes in the nervous system

Published data and our own results on the identification, cultivation, and potential therapeutic utilization of regional stem cells from humans and animals are reviewed. Pluripotent stem cells have been shown to proliferate in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampal formation in adult human and animal brains. Data on the hierarchical organization of genetic networks in controlling individual development suggest a possible functional role for repeat mini-and microsatellite DNA sequences in stem cell differentiation. Methods of using human bone marrow as a source of stem cells for restoring damaged tissue in the brain are discussed. Heat-shock proteins have been found to block the formation of glial scars after neural transplantation. The viability of stem cells after transplantation can be increased by transfer of genes for neurotrophic growth factors into the genomes of the neurons undergoing transplantation. __________ Translated from Morfologiya, Vol. 127, No. 3, pp. 7–16, May–June, 2005. Corresponding Member of the Russian Academy of Sciences     

组织激肽释放酶家族、激肽释放酶-激肽原-激肽系统及其重要应用

目前已明确,人组织激肽释放酶基因家族至少由15个基因组成,都定位于19q13.3～13.4,在基因结构、蛋白水平及三级结构上都有明显同源性。本文总结了组织激肽释放酶基因家族、激肽释放酶-激肽原-激肽系统的研究近况,并介绍了其在心血管疾病和肿瘤方面的重要应用。     

Potential therapeutic strategies to halt viral neuroinvasion

The viral infection of the central nervous system is a significant public health concern. So far, most clinical cases of viral neuroinvasion are dealt with supportive and/or symptomatic treatments due to the unavailability of specific treatments. Thus, developing specific therapies is required to alleviate neurological symptoms and disorders. In this review, we shed light on molecular aspects of viruses' entry into the brain which upon targeting with specific drugs have shown promising efficacy in vitro and in preclinical in vivo model systems. Further assessing the therapeutic potential of these drugs in clinical trials may offer opportunities to halt viral neuroinvasion in humans.     

New treatment strategies for ulcerative colitis

Introduction: Therapeutic strategies in ulcerative colitis are evolving. A personalized and optimal use of available drugs and the integration of new drug classes are the cornerstones underpinning the new treatment paradigms.

Areas covered: A structured literature search in Medline and PubMed, Cochrane meta-analyses, and abstracts of international congresses has been performed to review therapeutic approaches to ulcerative colitis. The primary therapeutic objective of therapy is to achieve clinical remission since persistence of active disease, even if mild, leads to a significant reduction in quality of life. Current treatment paradigms of ulcerative colitis are based on the use of 5-aminosalycilates, corticosteroids, thiopurines, TNF-α inhibitors and α4ß7 integrin blockers. The main determinants for drug class selection are disease extension, disease severity, and previous drug history. New drug classes that will likely become available in the foreseeable future include inhibitors of Janus kinases, modulators of sphingosine-1-phosphate receptors, SMAD-7 antisense oligonucleotides, interleukin-12/23 blockers, and fecal microbiota transplantation.

Expert commentary: Increasing therapeutic options for ulcerative colitis make predictors of response highly relevant. While these are not available, judicious use of therapies, avoidance of underdosing, or persistent therapy when criteria for drug failure are met are essential.