表皮生长因子受体靶向的RNA干扰在肺癌治疗中的研究现状

RNA干扰(RNA interference,RNAi)是近年来发现的一种由于mRNA被降解或者翻译沉默而引起的基因沉默的现象,并成为一种常用的研究基因功能、寻找医学顽症如肿瘤治疗方法的实验室技术.表皮生长因子受体(epidermal growth factor receptor,EGFR)在很多人类恶性肿瘤中过度表达,且EGFR信号通路启动后可促进细胞增殖、转移、血管生成以及阻断细胞凋亡,因此被作为开发肿瘤治疗方法的新靶点.本文就RNAi的研究现状及EGFR靶向的RNAi在肺癌治疗中的研究进展作一综述.     

RNA干扰技术及其在胃癌基因治疗中的应用进展

RNA干扰(RNAi)是指生物体内由双链RNA(dsRNA)介导同源mRNA的特异性降解,从而导致基因沉默的现象。目前,随着RNA干扰分子机制研究的不断深入,RNAi技术已广泛用于各种肿瘤的研究,尤其在胃癌治疗中的研究取得了重要进展,具有潜在、广阔的应用前景。     

RNA干扰技术与肿瘤研究进展

双链RNA能特异性地干扰(抑制)基因的功能,使内源性mRNA降解、导致基因沉默,这种现象称为RNA干扰(RNAi)。RNAi是近年来兴起的分子生物学技术,为肿瘤的基因治疗提供了一种有应用潜力的新途径。本文主要综述RNAi现象及其在肿瘤基因治疗研究方面的有关进展?     

RNA干扰技术在胰腺癌基因治疗中的应用

RNA干扰(RNAi)是双链RNA(dsRNA)介导的、由特异性引起的转录后基因沉默现象. RNA干扰技术作为基因沉默的有效手段,在肿瘤治疗方面显示出良好的前景.现就RNA干扰的机制、双链RNA的设计、小干扰RNA(siRNA)的制备方法和RNA干扰技术在胰腺癌治疗研究中的应用进展作一综述.     

RNA干扰在白血病基因治疗中的应用前景

RNA干扰(RNAi)作为一种进化保守的转录后基因沉默机制,是指双链RNA分子(dsRNA)被切割成21～23个核苷酸的小干扰RNA(siRNA),最终使其同源的mRNA特异性降解.RNAi现广泛用于多个生物体的功能基因组学研究,以及在基因表达异常导致的多种疾病的临床前模型中进行干预治疗.大约50%的白血病伴有异常基因的表达,利用RNAi肿瘤特异性基因靶向治疗为治疗白血病提供了一条新途径.随着siRNA在活体中的稳定性和转染效率的提高、非特异性作用的减少,正迅速应用于临床中.     

慢病毒表达系统介导的RNAi技术靶向沉默Bi-1基因对鼻咽癌细胞生物学特性的影响

目的探讨Bi-1基因的生物学功能及其与鼻咽癌发生与发展的相关性。方法首先构建以Bi-1为靶基因的RNA干扰(RNAi)质粒载体,采用慢病毒表达系统将其导入细胞,利用RNAi技术在细胞内诱导特异序列的基因沉默以观察对鼻咽癌细胞生长增殖的影响。结果靶向Bi-1沉默的慢病毒感染鼻咽癌细胞后能有效抑制细胞的生长增殖并诱导其凋亡,在荧光显微镜下可见经靶向Bi-1沉默的慢病毒处理后的鼻咽癌细胞呈现出细胞皱缩、核固缩、核断裂等典型的凋亡细胞形态,而且DNA凝胶电泳图谱呈现"梯状"现象;此外,Bi-1基因的沉默可有效地抑制裸鼠鼻咽癌移植瘤的生长。结论靶向沉默鼻咽癌细胞中的Bi-1表达,可抑制细胞生长增殖,并诱导细胞发生凋亡。     

RNA干扰及其在肿瘤研究中的应用进展

双链RNA(double-Stranded RNA,dsRNA)能特异性地抑制基因的功能,使内源性mRNA降解,导致基因沉默,这种现象称为RNA干扰(RNA interference,RNAi)。与其它传统的方法相比,小干扰RNA(Small interfering RNAs,or short interference RNAs,siRNAS)具有更好的抑制效果。RNAi的应用为研究肿瘤的基因功能提供了新的方法,并可能用于基因的特异治疗。     

RNAi及其与丙型肝炎基因治疗的研究进展

RNA干扰(RNAi)是通过双链RNA被核酸酶切割形成21—25nt的干扰性小RNA,即siRNA,由siRNA介导识别并靶向切割同源性靶mRNA分子而实现的基因沉默。最近有若干将RNAi技术应用于丙型肝炎基因治疗的研究,证实其不仅对丙型肝炎病毒RNA的复制和蛋白表达具有明显抑制作用,还能通过抑制Fas基因的表达,减轻肝细胞凋亡引起的损伤。     

RNA干扰在疾病治疗中的研究及应用进展

RNA干扰(RNAi)是指由双链RNA(dsRNA)所诱发的转录后水平上的基因沉默.RNAi通过小干扰RNA(siRNA)、重复相关siRNA(rasiRNA)和微小RNA(miRNA)而产生.由于RNAi对靶基因沉默作用的高度特异性和高效性,因此近年来RNAi用于肿瘤性疾病、感染性疾病、神经系统疾病等疾病的治疗研究是一个热点.虽然目前已有部分RNAi药物进入临床试验阶段,但是绝大部分的研究尚处于实验阶段,RNAi在临床上的实际应用尚需时日.     

RNAi及其在肝癌治疗中的作用

RNA干扰(RNAi)是指生物体内利用双链RNA诱导同源靶基因的mRNA特异性降解,导致转录后基因沉默的现象.近年来,RNA干扰技术在医学研究中的广泛应用取得显著的基因沉默效果,RNAi以其高特异性、高效性等显著优势将成为研究基因功能的新手段.此文综述该技术的发现、定义、机制、特征等及其在肝癌治疗中的应用.     

RNA干扰在胃癌基因治疗研究中的应用

RNA干扰(RNAi)能够特异而有效地阻断靶基因的表达,目前已广泛应用于生物体基因表达、调控与功能等的研究中。在胃癌方面,针对幽门螺杆菌感染与胃癌发病、胃癌化疗多药耐药、胃癌相关基因及治疗等都有许多积极的研究探索。本文在简述RNAi的基础上,综述其在胃癌基因治疗方面的研究和应用新进展。     

RNA干扰在胃癌治疗中的研究及应用

RNA干扰（RNAi）又称转录后基因沉默,是一种特异而有效的阻断靶基因表达的新技术。目前广泛地应用于生物体基因功能研究和多种肿瘤研究。在胃癌方面,针对胃癌化疗多药耐药、胃癌相关基因功能及胃癌基因治疗等进行了积极的探索,并取得了一些突破性的进展。     

Both treated and untreated tumors are eliminated by short hairpin RNA-based induction of target-specific immune responses

RNA interference (RNAi) for cancer treatment relies on the ability to directly kill cancer cells via down-regulation of target genes, but issues of delivery and efficacy have limited clinical adoption. Furthermore, current studies using immune-deficient animal models disregard potential interactions with the adaptive immune system. It has previously been observed that certain viral antigens appear to be more rapidly presented to the immune system than normal proteins due to the production of defective ribosomal products by the virus. Given that RNAi could potentially result in the generation of truncated mRNAs, we wondered whether a similar mechanism of immune presentation of a target gene was possible. Here we show that RNAi-cleaved mRNAs can be translated into incomplete protein, and if cleavage was downstream of cytotoxic T cell epitopes, resulted in increased presentation of target protein and the generation of a tumor-protective immune response. We show that mice inoculated with tumor cells treated with such short hairpin RNAs (shRNAs) were protected from subsequent challenge with untreated tumors. However, protection was only found if shRNAs were targeted downstream of the dominant cytotoxic T cell (CTL) epitope. Our work suggests that RNAi can alter immunity to targets and shows that not all tumor cells require direct RNAi exposure for treatment to be effective in vivo, pointing the way to a new class of RNAi-based therapy.     

Generation of single and double knockdowns in polarized epithelial cells by retrovirus-mediated RNA interference

RNA interference (RNAi) is a ubiquitous mechanism of eukaryotic gene regulation that can be exploited for specific gene silencing. Retroviruses have been successfully used for stable expression of short hairpin RNAs in mammalian cells, leading to persistent inhibition of gene expression by RNAi. Here, we apply retrovirus-mediated RNAi to epithelial Madin-Darby canine kidney cells, whose properties limit the applicability of other RNAi methods. We demonstrate efficient suppression of a set of 13 target genes by retroviral coexpression of short hairpin RNAs and a selectable marker. We characterize the resulting knockdown cell populations with regard to composition and stability, and examine the usefulness of proposed guidelines for choosing RNAi target sequences. Finally, we show that this system can be used to simultaneously target two genes, giving rise to double knockdowns. Thus, retrovirus-mediated RNAi is a convenient method for gene silencing in Madin-Darby canine kidney cells, and is likely to be applicable to virtually any mammalian cell.     

RNAi在胃癌相关基因功能研究和治疗方面的应用

胃癌是我国的主要恶性肿瘤之一,其死亡率占所有恶性肿瘤的23%左右,居各类癌症死亡率的首位。近年来,RNA干扰(RNAi)作为新兴技术,在针对胃癌相关基因功能研究及治疗方面的应用有着广阔的前景。     

RNA interference microarrays: high-throughput loss-of-function genetics in mammalian cells

RNA interference (RNAi) is a biological process in which a double-stranded RNA directs the silencing of target genes in a sequence-specific manner. Exogenously delivered or endogenously encoded double-stranded RNAs can enter the RNAi pathway and guide the suppression of transgenes and cellular genes. This technique has emerged as a powerful tool for reverse genetic studies aimed toward the elucidation of gene function in numerous biological models. Two approaches, the use of small interfering RNAs and short hairpin RNAs (shRNAs), have been developed to permit the application of RNAi technology in mammalian cells. Here we describe the use of a shRNA-based live-cell microarray that allows simple, low-cost, high-throughput screening of phenotypes caused by the silencing of specific endogenous genes. This approach is a variation of "reverse transfection" in which mammalian cells are cultured on a microarray slide spotted with different shRNAs in a transfection carrier. Individual cell clusters become transfected with a defined shRNA that directs the inhibition of a particular gene of interest, potentially producing a specific phenotype. We have validated this approach by targeting genes involved in cytokinesis and proteasome-mediated proteolysis.     

RNA interference--small RNAs effectively fight viral hepatitis.

RNA interference (RNAi) is the process of sequence-specific gene silencing, initiated by double-stranded RNA that is homologous in sequence to the target gene. This unique phenomenon has been extensively investigated during the last few years not only in the context of its mechanism and its possible role in the regulation of gene expression and cell function, but also as a potential powerful tool for gene therapy. Targeting essential viral genes or oncogenic alleles are only some of the possible applications of RNAi in the field of gene-directed therapy. This review covers the potential use of RNAi against hepatitis B and hepatitis C viruses, the main pathogens causing chronic liver disease. The major milestones along the discovery of RNAi will also be covered.     

胃癌基因治疗靶点的研究进展

RNA干扰(RNAi)是近几年来发现的研究生物体基因表达、调控与功能的一项崭新技术,近几年许多研究应用siRNA(small interfering RNA)对胃癌相关的致癌因子进行RNA干扰,在体内和体外试验中均产生了明显效果,从而促进了胃癌基因治疗研究的快速发展。随着研究进展更多的与胃癌相关的致癌因子和抑癌因子被发现,并成为胃癌基因治疗的新靶点。