RNA干扰

RNA干扰(RNAinterference,RNAi)是一种古老的生物抗病毒机制,能介导序列特异性的mRNA降解,是基因功能研究和蛋白组学的有效工具,在药物靶基因的筛选、抗病毒、肿瘤基因治疗等领域有很好的发展前景。     

Intrinsic Interference: a New Type of Viral Interference

The hemadsorption-negative plaque test has revealed a new type of viral interference, termed intrinsic interference. Several unrelated types of noncytopathic viruses were shown to induce in infected host cells a state of interference unique in being directed solely against superinfection by Newcastle disease virus (NDV). The NDV-refractory state arises only in those individual cells of a population actually infected by the inducing virus, and presumably results from the action of a protein(s) coded for by the viral genome. Thus, intrinsic interference differs fundamentally from that mediated by an extrinsic protein detectable under conditions favoring resistance to a broad spectrum of viruses and characteristic of interference induced by interferon, the latter being coded for by the cell genome. Intrinsic interference is defined as a viral genome-induced cellular state of resistance to challenge by high multiplicities of NDV, coexistent with a state of susceptibility to a broad spectrum of other viruses, similarly tested at high multiplicities. The capacity to induce intrinsic interference was demonstrated with rubella virus, Sindbis virus (arbovirus, group A), West Nile virus (arbovirus, group B), poliovirus (MEF, type 2), the lactic dehydrogenase virus (Riley's agent), and an unidentified nonhemadsorbing, noncytopathic adventitious virus. A state of intrinsic interference was also observed in the V5 line of mouse cells carrying a murine leukemia virus, probably resulting from some heretofore unsuspected contaminating virus. The molecular basis for intrinsic interference is not known, but it appears to involve a step in the NDV growth cycle beyond that of viral attachment, entry, and eclipse.     

慢病毒载体介导的RNA干扰

RNA干扰(RNAinterference)是指由双链RNA分子抑制同源基因的表达。慢病毒载体(lentivirusvector)则是高效的基因转导工具,能将外源序列稳定导入分裂相和非分裂相细胞。将慢病毒载体和RNA干扰结合,能在哺乳动物各类细胞中,特异性抑制同源基因的表达;也是基因功能研究和基因治疗的有力手段。     

RNA干扰技术治疗疾病

RNA干扰(RNA interference,RNAi)现象最早发现于秀丽隐杆线虫(Caenorhabditis elegans),随后发现该现象普遍存在于真菌、植物和哺乳动物等真核生物,并行使基因调控和抵御外源基因片段侵袭的作用。目前,RNAi分子机制和RNAi在基因功能方面的研究已经取得了突破性的进展。鉴于RNAi在基因沉默中的特异性、高效性和易操作,其在药物筛选和疾病治疗等方面有着广泛的应用前景。然而,RNAi技术用于治疗疾病的安全性尚待确定,分子传递途径也有待进一步的研究。     

噬菌体phi29 pRNA载体在RNA干扰中的初步应用研究

RNA干扰是在细胞胞质中双链RNA(dsR-NA)介导的序列特异性mRNA的降解[1]。这个过程是由21~25个被称为小干扰RNA(si RNA)形成的dsRNA完成[2]。目前,这一技术已经广泛应用于研究基因的功能,病毒感染治疗等方面。但是,si RNA在体内容易降解,干扰作用持续的时间不长。新的研究表明枯     

Delivery of RNA Interference

Over the last few years, RNA Interference (RNAi), a naturally occurring mechanism of gene regulation conserved in plant and mammalian cells, has opened numerous novel opportunities for basic research across the field of biology. While RNAi has helped accelerate discovery and understanding of gene functions, it also has great potential as a therapeutic and potentially prophylactic modality. Challenging diseases failing conventional therapeutics could become treatable by specific silencing of key pathogenic genes. More specifically, therapeutic targets previously deemed “undruggable” by small molecules, are now coming within reach of RNAi based therapy. For RNAi to be effective and elicit gene silencing response, the double-stranded RNA molecules must be delivered to the target cell. Unfortunately, delivery of these RNA duplexes has been challenging, halting rapid development of RNAi-based therapies. In this review we present current advancements in the field of siRNA delivery methods, including the pros and cons of each method.     

RNA干涉技术(RNAi)应用研究进展

RNA干涉是通过双链RNA的介导特异性地降解相应序列的mRNA,从而导致转录后水平的基因沉默,这一过程在拟南芥、线虫和真菌等多种模式植物中发现。RNAi是研究多种生物基因功能的有效手段,本文综述了RNA干涉的分子机理及其应用研究进展。     

Bacterial Interference with L-Forms

During the course of studying the effect of normal nasal flora on the growth of L-forms, a clear zone of inhibition was observed around colonies of many coagulase-negative staphylococci. Subsequent investigation demonstrated that Staphylococcus aureus and some S. albus strains produce a substance which is capable of markedly inhibiting the growth of stable staphylococcal and streptococcal L-forms. This interfering substance is separable from the staphylococcal organism and is diffusible through 1.5% agar, but not through a dialysis membrane. It is heat-stable.     

RNA Interference and Development

RNA interference consists in specific mRNA degradation in response to introduction of a double-stranded RNA, homologous in nucleotide sequence. RNA interference was found in eukaryotes and is used in genomics as a powerful method to determine the functions of genes with known nucleotide sequences. RNA interference is considered as a tool of protection against viruses and harmful consequences of mobile elements' transposals. The involvement of the components of RNA interference is considered in spermatogenesis of Drosophila melanogaster and regulation of the expression of genes in Caenorhabditis elegans responsible for temporal patterns of development. The role of RNA interference in stem cell formation and functioning is also considered.     

RNA干扰的研究进展

RNA干扰(RNA interference,RNAi)是一种由双链RNA诱发的转录后水平的基因沉默现象,是近几年发展起来的基因表达调节新机制。RNAi广泛存在于真菌、植物和动物中,这种调控可以由siRNA、shRNA及miRNA等小分子RNA参与。在此主要对RNAi的研究进展如背景、分子调控机制、存在的问题和应用前景等进行了综述。     

Allometric Effects on Plant Interference

The way interference develops in even-aged monocultures is usuallyjudged from the progression of weight-density curves that thestands exhibit. For whole plant weight-density curves this developmentof interference is unaffected by root:shoot allometric changesin themselves. However, for weight (of a plant part) - densitycurves, e.g. shoot weight - density curves, differing root:shootallometries in populations can change the way in which interferencedevelops. For example, in shoot weight-density curves, increasingthe proportion of total weight which is root increases the areaoccupied by an isolated plant and so decreases the density atwhich interference becomes appreciable. Increasing the proportionof total weight which is shoot, as density increases, increasesthe area occupied by an isolated plant but also decreases therate at which density constrains shoot weight. Interference, allometry, root:shoot ratio, competition     

RNAi在抗病毒防治领域的应用

RNAi是由双链RNA(dsRNA)所诱发的转录后水平上的基因沉默.由于对靶基因沉默作用的高度特异性和高效性,因此近年来用于肿瘤性疾病、感染性疾病、遗传性疾病等疾病的基因治疗研究,特别是在抗病毒领域的研究更是成为其应用热点之一.虽然目前RNAi已经较为广泛地应用于动物病毒及各种疾病病毒的基因治疗研究中,但其在应用过程中还有许多亟待解决的问题.本文就RNAi及其在抗病毒领域的应用研究和其存在的问题展开综述.     

dsRNA介导的RNA干扰

在多种生物中 ,外源或内源性的双链ＲＮＡ(ｄｏｕｂｌｅ ｓｔｒａｎｄｅｄＲＮＡ ,ｄｓＲＮＡ)导入细胞中 ,与ｄｓＲＮＡ同源的ｍＲＮＡ则受到降解 ,因而其相应的基因受到抑制。这种转录后基因沉默 (ｐｏｓｔ ｔｒａｎｓｃｒｉｐｔｉｏｎａｌｇｅｎｅｓｉｌｅｎｃｉｎｇ ,ＰＴＧＳ)机制首先在线虫 (Ｃ .ｅｌｅｇａｎｓ)中得以证实。由于这是一种在ＲＮＡ水平的基因表达抑制 ,故也称为ＲＮＡ干扰 (ＲＮＡｉｎｔｅｒｆｅｒ ｅｎｃｅ) ,简称ＲＮＡｉ[1] 。随后发现 ,在各种生物 ,如果蝇[2 ] 、拟南芥菜[3 ] 、及小鼠[4] 等均存在ｄｓＲＮＡ介导…     

Interference competition and parasite virulence

Within-host competition between parasites, a consequence of infection by multiple strains, is predicted to favour rapid host exploitation and greater damage to hosts (virulence). However, the inclusion of biological variables can drastically change this relationship. For example, if competing parasite strains produce toxins that kill each other (interference competition), their growth rates and virulence may be reduced relative to single-strain infections. Bacteriocins are antimicrobial toxins produced by bacteria that target closely related strains and species, and to which the producing strain is immune. We investigated competition between bacteriocin-producing, insect-killing bacteria (Photorhabdus and Xenorhabdus) and how this competition affected virulence in caterpillars. Where one strain could kill the other, and not vice versa, the non-killing strain was competitively excluded, and insect mortality was the same as that of the killing strain alone. However, when caterpillars were multiply infected by strains that could kill each other, we did not observe competitive exclusion and their virulence was less than single-strain infections. The ubiquity and diversity of bacteriocins among pathogenic bacteria suggest mixed infections will be, on average, less virulent than single infections.     

RNA干涉的最新研究进展

RNA干涉 (RNAi)是将双链RNA(dsRNA)导入细胞引起特异基因mRNA降解的一种细胞反应过程 .它是转录后基因沉默 (PTGS)的一种 .RNAi在生物界中广泛存在 .RNAi发生过程主要分为 3个阶段 :起始阶段 ,扩增阶段 ,效应阶段 .RNAi在维持基因组稳定、保护基因组免受外源核酸侵入、基因表达调控等方面发挥重要生物学作用 .RNAi作为基因沉默的一个工具 ,已被广泛用于基因功能研究、基因治疗和新药研究与开发等方面 .