共查询到20条相似文献,搜索用时 15 毫秒
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Silencing gene expression through a process known as RNA interference (RNAi) has been known in the plant world for many years. In recent years, knowledge of the prevalence of RNAi and the mechanism of gene silencing through RNAi has started to unfold. It is now believed that RNAi serves in part as an innate response against invading viral pathogens and, indeed, counter silencing mechanisms aimed at neutralizing RNAi have been found in various viral pathogens. During the past few years, it has been demonstrated that RNAi, induced by specifically designed double-stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Furthermore, it is now apparent that in in vitro and in some in vivo models, the prospects for this technology in developing therapeutic applications are robust. However, many key questions and obstacles in the translation of RNAi into a potential therapeutic platform still remain, including the specificity and longevity of the silencing effect, and, most importantly, the delivery of the dsRNA that induces the system. It is expected that for the specific examples in which the delivery issue could be circumvented or resolved, RNAi may hold promise for the development of gene-specific therapeutics. 相似文献
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RNA干扰的研究进展 总被引:8,自引:0,他引:8
RNA干扰是指外源双链RNA进入细胞后引起与其同源的mRNA特异性降解的现象,它是真核生物在长期进化中形成的一种保守的防御机制,对真核生物有着重要的意义,它参与真核生物抵御病毒侵染、阻断转座子的异常活动,调控基因表达。RNA干扰已成为一种进行基因功能分析的强有力的工具,并有望成为最有潜力的基因干预治疗方法。 相似文献
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RNA干涉的研究进展 总被引:34,自引:0,他引:34
生物体内导入双链RNA后会引起体内同源基因特异性的沉默,这种现象称为RNA干涉,本主要介绍RNA干涉的研究历史,作用机制和应用等方面的情况。 相似文献
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RNA干扰在疾病治疗方面的应用研究 总被引:1,自引:0,他引:1
RNA干扰是由双链RNA引起的序列特异的基因沉默现象。由于RNA干扰能在细胞组织及动物模型中沉默疾病相关基因,因此,RNA干扰也是各种疾病治疗的有效手段。在哺乳动物细胞内诱导RNA干扰可以通过导入小干扰RNA(siRNA),或是以质粒、病毒为载体表达短的发夹RNA(shRNA)而实现。本文介绍了RNA干扰在疾病治疗方面的应用,并就其面临的挑战进行讨论。 相似文献
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Popescu FD 《Journal of cellular and molecular medicine》2005,9(4):840-853
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Immunotherapeutic strategies employing RNA interference technology
for the control of cancers 总被引:1,自引:0,他引:1
Summary The human immune system is comprised of several types of cells that have the potential to eradicate tumors without inflicting
damage on normal tissue. Over the past decade, progress in the understanding of tumor biology and immunology has offered the
exciting possibility of treating malignant disease with vaccines that exploit the capacity of T cells to effectively and selectively
kill tumor cells. However, the immune system frequently fails to mount a successful defense against cancers despite vaccination
with tumor-associated antigens. The ability of these vaccines to generate an abundant supply of armed effector T cells is
often limited by immunoregulatory signaling pathways that suppress T cell activation. In addition, many tumors create a local
microenvironment that inhibits the function of T cells. The attenuation of these pathways, which facilitate the evasion of
tumors from immune surveillance, thus represents a potentially effective approach for cancer immunotherapy. Specifically,
it may be of interest to modify the properties of dendritic cells, T cells, and tumor cells to downregulate the expression
of proteins that diminish the immune response to cancers. RNA interference (RNAi) techniques have developed into a highly
effective means of intracellular gene ‘knockdown’ and may be successfully employed in this way to improve cancer immunotherapies.
This strategy has recently been explored both in vitro and in vivo, and has generated significantly enhanced antitumor immunity in numerous studies. Nevertheless, several practical concerns
remain to be resolved before RNAi technology can be implemented safely and efficiently in humans. As novel developments and
discoveries in molecular biology rapidly continue to unfold, it is likely that this technology may soon translate into a potent
form of gene silencing in the clinic with profound applications to cancer immunotherapy. 相似文献
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RNA interference (RNAi) was quantitatively evaluated from a kinetic viewpoint. A simple kinetic evaluation based on moment analysis was proposed, assuming suppression and recovery phases of gene expression. We defined the area under the curve of the inhibitory effect (AUC(IE)) as an index of the total intensity of RNAi and the mean response time of the inhibitory effect (MRT(IE)) as an index of its duration. The proposed kinetic analysis helps to understand the RNAi effect in a quantitative and time-dependent manner, which will be beneficial for designing RNAi-based gene silencing for both experimental and therapeutic purposes. 相似文献
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The large number of candidate genes identified by modern high-throughput technologies require efficient methods for generating knockout phenotypes or gene silencing in order to study gene function. RNA interference (RNAi) is an efficient method that can be used for this purpose. Effective gene silencing by RNAi depends on a number of important parameters, including the dynamics of gene expression and the RNA dose. Using mouse hepatoma cells, we detail some of the principal characteristics of RNAi as a tool for gene silencing, such as the RNA dose level, RNA complex exposure time, and the time of transfection relative to gene induction, in the context of silencing a green fluorescent protein reporter gene. Our experiments demonstrate that different levels of silencing can be attained by modulating the dose level of RNA and the time of transfection and illustrate the importance of a dynamic analysis in designing robust silencing protocols. By quantifying the kinetics of RNAi-based gene silencing, we present a model that may be used to help determine key parameters in more complex silencing experiments and explore alternative gene silencing protocols. 相似文献
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Dhandapani Gurusamy Kanakachari Mogilicherla Jayendra Nath Shukla Subba Reddy Palli 《Archives of insect biochemistry and physiology》2020,104(4):e21678
RNA interference (RNAi) is a valuable method for understanding the gene function and holds great potential for insect pest management. While RNAi is efficient and systemic in coleopteran insects, RNAi is inefficient in lepidopteran insects. In this study, we explored the possibility of improving RNAi in the fall armyworm (FAW), Spodoptera frugiperda cells by formulating dsRNA with Cellfectin II (CFII) transfection reagent. The CFII formulated dsRNA was protected from degradation by endonucleases present in Sf9 cells conditioned medium, hemolymph and midgut lumen contents collected from the FAW larvae. Lipid formulated dsRNA also showed reduced accumulation in the endosomes of Sf9 cells and FAW tissues. Exposing Sf9 cells and tissues to CFII formulated dsRNA caused a significant knockdown of endogenous genes. CFII formulated dsIAP fed to FAW larvae induced knockdown of iap gene, growth retardation and mortality. Processing of dsRNA into siRNA was detected in Sf9 cells and Spodoptera frugiperda larvae treated with CFII conjugated 32P-UTP labeled dsGFP. Overall, the present study concluded that delivering dsRNA formulated with CFII transfection reagent helps dsRNA escapes from the endosomal accumulation and improved RNAi efficiency in the FAW cells and tissues. 相似文献
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Within the course of only the last few years, RNA interference (RNAi) has been established as a standard technology for investigation of protein function and target validation. The present review summarizes recent progress made in the application of RNAi in neurosciences with special emphasis on pain research. RNAi is a straightforward method to generate loss-of-function phenotypes for any gene of interest. In mammals, silencing is induced by small interfering RNAs (siRNAs), which have been shown to surpass traditional antisense molecules. Due to its high specificity, RNAi has the potential for subtype selective silencing of even closely related genes. One of the major challenges for in vivo investigations of RNAi remains efficient delivery of siRNA molecules to the relevant tissues and cells, particularly to the central nervous system. Various examples will be given to demonstrate that intrathecal application of siRNAs is a suitable approach to analyse the function of receptors or other proteins that are hypothesized to play an important role in pain signalling. Intensive efforts are currently ongoing to solve remaining problems such as the risk of off-target effects, the stability of siRNA molecules and their efficient delivery to the CNS. RNAi has thus demonstrated that it is an extremely valuable tool for the development of new analgesic drugs. 相似文献