RNA干扰在疾病治疗上的应用

RNA干扰(RNA interference,RNAi)是一种双链RNA分子在mRNA水平上引发的特异性基因沉默现象。RNAi在基因治疗方面表现出了光明的前景,已成功地应用于多种疾病的临床治疗。本文主要介绍了RNAi在疾病治疗上的应用及研究进展。     

RNA干扰用于基因治疗的研究进展

RNA干扰(RNAi)是20世纪末才被人们认识和重视的一种通过双链RNA抵御病毒入侵或抑制转座子活动的生物防御机制。随着RNA干扰分子机制研究的深入及其应用研究的发展,人们发现RNA干扰技术在基因功能研究及人类疾病的基因治疗上具有广阔的应用前景。本文在简述RNAi分子机制的基础上,综述了RNAi在抗病毒治疗及抗肿瘤治疗方面的研究和应用概况。     

RNAi技术及其在口腔医学研究中的应用

RNAi(RNA interference)技术在医学研究中的应用发展迅速,运用RNAi可用来进行特定基因功能的研究和特异性基因治疗,在包括肿瘤、遗传性疾病、发育性疾病、病毒感染等的发病、预防、治疗方面的研究有着广阔的应用前景.本文就RNAi技术及其在口腔医学领域研究中的应用现状和前景做一综述.     

RNA干扰技术在基因治疗中的应用进展

RNA干扰(RNA interference,RNAi)是一种双链RNA分子在mRNA水平上关闭相应序列基因的表达或使其沉默的过程,在基因治疗方面有着无可比拟的优势,已成功的应用于肿瘤、病毒感染、遗传性疾病及神经系统疾病等重大疾病的治疗.本文将主要介绍siRNA基因治疗的导入方法与途径,以及在不同疾病中,RNAi技术进行基因治疗的应用.     

RNAi在基因缺陷模型方面的应用

RNA干扰(RNA interference,RNAi)是指双链RNA(double-stranded RNA,dsRNA)分子导入细胞内后,促进与之同源的mRNA发生特异性的降解,从而高效并特异地阻断或抑制相应基因表达活性的现象。RNAi技术现已成为调控基因的表达,阐明细胞的信号通路和研究功能基因组学的有力工具,并迅速在临床医学上展现出基因药物的诱人前景。目前,人们已开始对RNAi技术在人类疾病预防和治疗中的应用进行研究．这些研究涉及到病毒感染、癌症、代谢性疾患以及遗传病等各个方面。通过综述siRNA分子的作用机制、载体构建以及其在基因缺陷模型的建立等方面的应用,从而展示出RNAi在相关疾病的分子机制研究和基因治疗方面的诱人前景。     

RNA干扰技术及其在肝纤维化中的应用

RNA干扰(RNA interference,RNAi)是近几年发展起来的新技术,是外源和内源性双链RNA在生物体内诱导同源靶基因的mRNA特异性降解,因而抑制相应基因表达,导致转录后基因沉默的现象.尽管RNA干扰发现的时间较短,但由于其具有操作简单、成本低、特异性高和高效性等特点,因而发展迅速.小干扰RNA(small interfering RNA,siRNA)的可制备使RNAi在很多领域有了应用的前景,尤其是在复杂多变的肝脏疾病中.肝纤维化(hepatic fibrosis,HF)是多种慢性肝病发展的共同病理基础,RNAi技术在其基因治疗领域拥有广阔的前景.RNAi具有能够调节细胞增殖、抑制致病基因的表达、影响细胞的信号转导等方面的作用,可能成为肝纤维化有效的潜在治疗手段.     

慢病毒载体介导RNAi的研究进展

RNAi通过双链RNA的介导,特异性阻抑相关序列的表达,从而导致转录后水平的基因沉默.广泛存在于真菌、植物和动物等真核生物中.慢病毒载体是理想的真核细胞基因转移工具,被广泛应用于相关的RNAi研究领域,例如抗病毒研究、癌症及其治疗、遗传性疾病的治疗、基因治疗.现已发现,慢病毒载体能够介导组织特异、时间特异的RNAi,在疾病的基因靶向性治疗上必有广阔的前景.     

RNAi的抗病毒机制及应用

RNA干扰(RNA interference,RNAi)能够在转录水平、翻译水平和转录后水平上抑制病毒的复制,这为临床治疗病毒性疾病奠定了理论基础。近年来,RNAi技术发展迅速,使得RNAi技术应用于病毒性疾病的治疗成为可能。本文从RNAi抗病毒的作用机制及RNAi在抗动物病毒性疾病方面的应用等方面进行综述,并对RNAi在抗病毒方面的应用前景进行展望。     

RNA干扰药物用于疾病治疗的安全性问题

RNA干扰（RNA interference,RNAi）是指由双链RNA介导的序列特异的转录后基因沉默。RNAi技术因其特异性、高效性而备受青睐,在疾病治疗方面表现出广阔的应用前景。然而,近年来的研究发现,基于RNAi技术开发的药物存在安全性问题,主要包括引起免疫反应、产生脱靶效应、以及存在竞争微RNA通路等。这些问题的突破将使RNAi技术获得更加广泛的应用。     

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.     

RNA interference for antiviral therapy

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.     

Illuminating the silence: understanding the structure and function of small RNAs

RNA interference (RNAi) is triggered by double-stranded RNA helices that have been introduced exogenously into cells as small interfering (si)RNAs or that have been produced endogenously from small non-coding RNAs known as microRNAs (miRNAs). RNAi has become a standard experimental tool and its therapeutic potential is being aggressively harnessed. Understanding the structure and function of small RNAs, such as siRNAs and miRNAs, that trigger RNAi has shed light on the RNAi machinery. In particular, it has highlighted the assembly and function of the RNA-induced silencing complex (RISC), and has provided guidelines to efficiently silence genes for biological research and therapeutic applications of RNAi.     

RNAi mechanisms and applications

Within the past two decades we have become increasingly aware of the roles that RNAs play in regulation of gene expression. The RNA world was given a booster shot with the discovery of RNA interference (RNAi), a compendium of mechanisms involving small RNAs (less than 30 bases long) that regulate the expression of genes in a variety of eukaryotic organisms. Rapid progress in our understanding of RNAi-based mechanisms has led to applications of this powerful process in studies of gene function as well as in therapeutic applications for the treatment of disease. RNAi-based therapies involve two-dimensional drug designs using only identification of good Watson-Crick base pairing between the RNAi guide strand and the target, thereby resulting in rapid design and testing of RNAi triggers. To date there are several clinical trials using RNAi, and we should expect the list of new applications to grow at a phenomenal rate. This article summarizes our current knowledge about the mechanisms and applications of RNAi.     

RNA interference: an emerging generation of biologicals

RNA interference (RNAi) is a mechanism displayed by most eukaryotic cells to rid themselves of foreign double-stranded RNA molecules. RNAi has now been demonstrated to function in mammalian cells to alter gene expression, and has been used as a means for genetic discovery as well as a possible strategy for genetic correction. RNAi was first described in animal cells by Fire and colleagues in the nematode, Caenorhabditis elegans. Knowledge of RNAi mechanism in mammalian cell in 2001 brought a storm in the field of drug discovery. During the past few years scientists all over the world are focusing on exploiting the therapeutic potential of RNAi for identifying a new class of therapeutics. The applications of RNAi in medicine are unlimited because all cells possess RNAi machinery and hence all genes can be potential targets for therapy. RNAi can be developed as an endogenous host defense mechanism against many infections and diseases. Several studies have demonstrated therapeutic benefits of small interfering RNAs and micro RNAs in animal models. This has led to the rapid advancement of the technique from research discovery to clinical trials.     

Nanoparticle-mediated double-stranded RNA delivery system: A promising approach for sustainable pest management

RNA interference (RNAi) targeting lethal genes in insects has great potential for sustainable crop protection. Compared with traditional double-stranded (ds)RNA delivery systems, nanoparticles such as chitosan, liposomes, and cationic dendrimers offer advantages in delivering dsRNA/small interfering (si)RNA to improve RNAi efficiency, thus promoting the development and practice of RNAi-based pest management strategies. Here, we illustrate the limitations of traditional dsRNA delivery systems, reveal the mechanism of nanoparticle-mediated RNAi, summarize the recent progress and successful applications of nanoparticle-mediated RNAi in pest management, and finally address the prospects of nanoparticle-based RNA pesticides.     

Therapeutic potential of RNAi in metabolic diseases

Over the past years RNA interference (RNAi) has exploded as a new approach to manipulate gene expression in mammalian systems. More recently, RNAi has acquired interest as a potential therapeutic strategy. This review focuses on the potential therapeutic use of RNAi for metabolic diseases, the current understanding of RNAi biology, and how RNAi has been utilized to study the role of different genes in the pathogenesis of diabetes and obesity. Also reviewed are the in vivo proof-of-principle experiments that provide the preclinical justification for the development of RNAi-based therapeutics for diabetes and the key challenges that currently limit its application in the clinical setting.     

Modulation of angiogenesis with siRNA inhibitors for novel therapeutics

Cancer and many other serious diseases are characterized by the uncontrolled growth of new blood vessels. Recently, RNA interference (RNAi) has reinvigorated the therapeutic prospects for inhibiting gene expression and promises many advantages over binding inhibitors, including high specificity, which is essential for targeted therapeutics. This article describes the latest developments using small-interfering RNA (siRNA) inhibitors to downregulate various angiogenic and tumor-associated factors, both in cell-culture assays and in animal disease models. The majority of research efforts are currently focused on understanding gene function, as well as proof-of-concept for siRNA-mediated anti-angiogenesis. The prospects for siRNA therapeutics, both advantages and looming hurdles, are evaluated.