基于造血干细胞为靶细胞的基因治疗

在基因治疗中,造血干细胞因为具有自我更新及分化为各种血细胞系的能力而成为一种很有吸引力的靶细胞。将外源目的基因导入造血干细胞,以纠正或补偿因基因缺陷和异常引起的疾病,特别是血液疾病已取得重要进展,例如:腺苷脱氨酶缺陷病、血友病、地中海贫血症及镰状细胞性贫血症等。而慢病毒以其转染效率高,能够感染非分裂期细胞的特点成为转染造血干细胞的最适合载体,本文就造血干细胞的特性、载体的选择及临床应用和基因治疗的安全性等方面作一综述。     

基因治疗中的动物病毒载体

动物病毒载体在基因转移和治疗中有着重要意义。逆转录病毒载体是目前用子基因治疗最为成功的,已用于多种病例的临床研究;腺病毒载体成功地对多种基因进行了转移,并用于囊性纤维病的基因治疗临床研究;腺病毒相关病毒载体和单纯疤疾病毒载体介导的基因转移在体外培养细胞和动物实验中都取得成功,在某些疾病的基因治疗中显示出特殊的应用价值。     

基因治疗导入载体的研究进展

基因治疗在恶性肿瘤、癌症、遗传性疾病和心脑血管等疾病的治疗中开始应用,临床治疗效果明显。基因治疗中的关键技术是选用合适的载体将外源基因高效导入受体靶细胞,综述了基因治疗中病毒和非病毒载体的研究进展。     

造血干细胞基因治疗:进展与挑战

造血干细胞具有自我更新和分化为各类血细胞的潜能,一直被认为是最理想的基因治疗靶细胞之一.近年来,基于慢病毒载体的造血干细胞基因治疗逐渐进入临床.同时,随着CRISPR-Cas9等基因编辑技术的不断发展,第二代造血干细胞精准基因治疗研究已经取得重要进展,预计将逐渐开始临床转化.但目前,造血干细胞基因编辑还面临一些问题亟待解决,尤其是精准编辑效率还需要大幅度提高.     

慢病毒载体与造血干细胞介导的基因治疗

慢病毒载体不仅能感染造血干细胞 (HSCs) ,使携带的目的基因整合至HSCs基因组内 ,且能利用病毒携带的调控元件 ,使目的基因随HSCs细胞特异性表达 ,因此是一种有效的感染HSCs和进行基因治疗的工具。主要对慢病毒载体基因组特点、改建过程、慢病毒对干细胞的感染能力、慢病毒携带的目的基因在HSCs内的表达及调控等方面做了简要的综述     

可诱导慢病毒载体的优化策略及应用

以1型人免疫缺陷病毒(HIV-1)为基础构建的慢病毒载体具有可感染非分裂细胞、免疫反应小、携带的基因片段容量大和可整合进宿主基因组而长期表达等优点,因而成为最理想的基因转移载体之一。可诱导慢病毒载体介导的可诱导基因表达系统能够有效控制目的基因表达,扩大了慢病毒载体的临床应用潜能,成为很有前景的基因治疗载体。主要介绍带有四环素和其他几种诱导系统的可调控性慢病毒载体及其改进,以及可诱导慢病毒载体在RNA干扰中的应用。     

腺病毒载体研究新进展

近年来,病毒载体尤其是腺病毒载体的研究成为治疗研究中的一个热点。本综述了腺病毒载体的构建和应用方面的最新进展,表明腺病毒载体是基因转移的重要手段,具有众多的优点,在基因治疗领域具有广阔的应用前景。     

病毒--基因治疗中有效的载体系统

基因治疗面临的首要问题是如何选择适当的基因载体将具有治疗价值的基因导入靶细胞并使其有效表达,以达到治疗疾病的目的。目前基因治疗临床试验中采用的载体大多数为病毒载体。本文主要介绍基因治疗中常用的4种病毒载体的生物学特性,以及各个载体在基因治疗中的优缺点。     

腺病毒相关病毒载体的研究进展

实现基因治疗的关键在于目的基因的高效转移并适度表达,这将直接影响其治疗的效率和安全性。因此,探寻理想的基因转移载体显得尤为重要。腺病毒相关病毒（adeno-associated virus,AAV）是一种缺陷型的单链DNA病毒,既可以转染分裂细胞又可以转染非分裂细胞。AAV在宿主体内以定向整合的方式存在,AAV重组体在细胞内能长期稳定地表达,且在体内不引起明显的病理变化,表明AAV作为基因治疗的载体是安全、有效和可行的。     

基因治疗心肌缺血的载体应用新进展

近年来,随着基因治疗技术的不断进步,为心肌缺血的治疗开辟了一条全新的途径,并取得了一些令人鼓舞的进展。基因治疗主要包括治疗基因、基因转移载体以及基因导入途径三个方面。基因转移载体又在治疗基因和基因表达之间起着桥梁作用,因此,发展安全、高效的基因转移系统是基因治疗的关键之一。目前用于基因治疗心肌缺血基因转移的载体主要有病毒载体和非病毒载体。下面将就不同载体在心肌缺血的基因治疗中的应用进展进行简要的总结。     

Cauliflower mosaic virus protein P6-TAV plays a major role in alteration of aphid vector feeding behaviour but not performance on infected Arabidopsis

Emerging evidence suggests that viral infection modifies host plant traits that in turn alter behaviour and performance of vectors colonizing the plants in a way conducive for transmission of both nonpersistent and persistent viruses. Similar evidence for semipersistent viruses like cauliflower mosaic virus (CaMV) is scarce. Here we compared the effects of Arabidopsis infection with mild (CM) and severe (JI) CaMV isolates on the feeding behaviour (recorded by the electrical penetration graph technique) and fecundity of the aphid vector Myzus persicae. Compared to mock-inoculated plants, feeding behaviour was altered similarly on CM- and JI-infected plants, but only aphids on JI-infected plants had reduced fecundity. To evaluate the role of the multifunctional CaMV protein P6-TAV, aphid feeding behaviour and fecundity were tested on transgenic Arabidopsis plants expressing wild-type (wt) and mutant versions of P6-TAV. In contrast to viral infection, aphid fecundity was unchanged on all transgenic lines, suggesting that other viral factors compromise fecundity. Aphid feeding behaviour was modified on wt P6-CM-, but not on wt P6-JI-expressing plants. Analysis of plants expressing P6 mutants identified N-terminal P6 domains contributing to modification of feeding behaviour. Taken together, we show that CaMV infection can modify both aphid fecundity and feeding behaviour and that P6 is only involved in the latter.     

大肠杆菌多基因共表达策略

利用基因工程手段实现多个基因在同一宿主菌中共表达是大肠杆菌细胞发育调节研究和代谢途径改造的有效手段。介绍了单一转录单元的多基因共表达载体、多重转录单元的多基因共表达和单基因载体的构建原理、特点、优势及转化策略,并着重介绍了利用LIC衔接子实现基因在多基因载体上定位连接的原理和方法。     

Heterorhabditis bacteriophora as a vector for introducing its associated bacterium into the hemocoel of Galleria mellonella larvae

The nematode Heterorhabditis bacteriophora serves as a vector enabling its bacterial associate to reach the hemocoel of its host, the seventh-instar larva of Galleria mellonella. At 28.5°C, the LD₅₀s of the orally introduced nematode-bacterial complex and the intrahemocoelically injected bacteria are three to six nematodes and one to two cells, respectively.     

R~3中的一类拟齐次向量场的性质

利用三维拟齐次向量场和三维齐次向量场之间的等价关系并借鉴对齐次向量场的研究方法,把齐次向量场的一些结论推广到拟齐次向量场.并运用这些理论分析了具有不同增长率的三种群竞争模型的动力学性质和生物意义,得到增长率最大的种群在此竞争系统中占优,增长率最小的种群在此竞争系统中灭绝的结论.     

HIV-1载体的研发沿革

自从科学家于1983年发现了人类免疫性缺陷病毒1(human immunodeficiency virus1,HIV-1)以来,随着对它的研究不断深入,其表达载体的开发也有了长足的进步。与其他逆转录病毒载体相比,如莫罗尼小鼠白血病病毒(murine leukemiavirus,MLV)载体和泡沫病毒(foamyvirus,FV)载体等,HIV-1载体具有诸多独特的优点,因而有着更广泛的应用于临床基因治疗的前景。该文对HIV-1载体的研发过程及其优缺点进行综述。     

植物病毒载体在植病互作研究中的应用

在植物与病原菌互作的研究中,植物抗性基因和病原菌无毒基因的研究是两个重要的热点。利用植物病毒沉默载体构建的VIGS(Virus Induced Gene Silencing)体系研究植物的防御机制;利用植物病毒表达载体克隆和研究病原菌的无毒基因,将使我们更深刻地理解植物和病原菌互作的分子机理,最终为培育番茄白粉病持久抗性品种打下理论基础。对植物病毒载体的研究进行了综述并就我们承担的课题进行了讨论。     

Synthesis of diamine maleyl chitosans, and in vitro transfection studies

Three novel diamine-modified chitosan derivatives were synthesized from N-maleyl chitosan via Michael addition reaction with 1,2-diaminoethane, 1,4-diaminobutane, and 1,6-diaminohexane, respectively. These chitosan derivatives exhibited well binding ability of condensing plasmid DNA to form complexes with size ranging from 150 to 500 nm when the chitosan derivative/DNA weight ratios were above 10. The complexes observed by scanning electron microscopy (SEM) exhibited a compact and spherical morphology. The cytotoxicity of the chitosan derivatives presented a dependence on their side-chain structures. The gene transfection experiments were evaluated in 293 T and HeLa cells. The data obtained demonstrated that the gene transfection efficiencies of these chitosan derivatives were better than that of chitosan, suggesting these chitosan derivatives as potential gene vectors in vitro.     

Polymer‐coated viral vectors: hybrid nanosystems for gene therapy

The advantages and critical aspects of nanodimensional polymer‐coated viral vector systems potentially applicable for gene delivery are reviewed. Various viral and nonviral vectors have been explored for gene therapy. Viral gene transfer methods, although highly efficient, are limited by their immunogenicity. Nonviral vectors have a lower transfection efficiency as a result of their inability to escape from the endosome. To overcome these drawbacks, novel nanotechnology‐mediated interventions that involve the coating or modification of virus using polymers have emerged as a new paradigm in gene therapy. These alterations not only modify the tropism of the virus, but also reduce their undesirable interactions with the biological system. Also, co‐encapsulation of other therapeutic agents in the polymeric coating may serve to augment the treatment efficacy. The viral particles can aid endosomal escape, as well as nuclear targeting, thereby enhancing the transfection efficiency. The integration of the desirable properties of both viral and nonviral vectors has been found beneficial for gene therapy by enhancing the transduction efficiency and minimizing the immune response. However, it is essential to ensure that these attempts should not compromise on the inherent ability of viruses to target and internalize into the cells and escape the endosomes.     

纳米载体介导的植物遗传转化研究现状和前景

高效遗传转化技术是植物重要性状功能基因鉴定的前提和转基因育种的基础.随着纳米生物技术的发展,以纳米载体介导的植物转基因技术已显示出巨大的应用潜力.综述了国内外应用于植物纳米载体的类型、与外源基因的结合方式以及传输细胞的原理,重点阐述了影响纳米基因载体性能与转化效率的重要因素,以及纳米载体介导外源基因转化植物细胞的方法,...