本文選題：RNA干擾(RNAi) + 乙型肝炎病毒(HBV)　； 參考：《第一軍醫(yī)大學(xué)》2006年博士論文

【摘要】：乙型肝肝炎病毒(HBV)是一種長3.2Kb的DNA病毒，它幾乎在整個肝臟可以復(fù)制。雖然高活性的乙肝疫苗已問世20多年，但HBV感染仍然是一種危害全球健康的重大疾病。據(jù)統(tǒng)計全球約有3.5億的HBV感染者，而中國又是HBV感染的高發(fā)區(qū)，約有50％～70％的人群感染過HBV，其中約8％～12％的人群，即超過1億人口是乙肝表面抗原攜帶者，每年因急慢性HBV感染致死的人數(shù)約有一百萬之多。目前，干擾素和腺苷類似物是FDA批準的，僅有的幾種抑制HBV復(fù)制的藥物，但它們的作用效果都很有限。腺苷類似物如lamivudine和adefovir dipivoxil的作用原理是通過抑制HBV逆轉(zhuǎn)錄活性，而直接影響病毒復(fù)制的，雖然這類藥物能高效地清除血清中的HBV-DNA，但不能完全清除體內(nèi)感染的HBV，因此停止用藥后HBV會復(fù)發(fā)，，并且用藥時間的延長會導(dǎo)致HBV病毒突變體的產(chǎn)生。 RNA干擾(RNA interference，RNAi)技術(shù)是指內(nèi)源性或外源性雙鏈RNA(dsRNA)介導(dǎo)的，細胞內(nèi)mRNA發(fā)生特異性降解，并導(dǎo)致靶基因的表達沉默，產(chǎn)生相應(yīng)的功能表型缺失的一種現(xiàn)象。這一現(xiàn)象屬于轉(zhuǎn)錄后的基因沉默機制(Posttranscriptional gene silencing，PTGS)。在哺乳動物細胞中RNAi活性主要是通過21～23nt長的small interfering RNAs(siRNA)來實現(xiàn)的。研究表明siRNA已在很多領(lǐng)域顯示出對目的基因的清除作用，因此，RNAi也成為治療HBV感染的一種可選的重要手段。 自1998年2月，F(xiàn)ire和Mello兩位科學(xué)家首次在Nature上發(fā)表了：把dsRNA注射入一種線蟲(Caenorhabditis elegans)體內(nèi)，該dsRNA可以誘導(dǎo)基因靶向?qū)Ｒ恍缘幕虮磉_靜寂(gene silencing)等研究報告以來，許多研究工作者都先后用RNAi技術(shù)，在線蟲、果蠅、植物、動物卵細胞和哺乳類細胞中進行了大量研究，
[Abstract]:Hepatitis B virus (HBV) is a long 3.2Kb DNA virus that can be replicated almost throughout the liver. Although the highly active hepatitis B vaccine has been available for more than 20 years, HBV infection is still a major disease that endangers global health. According to statistics, there are about 350 million people living with HBV in the world, and China is also a high incidence area of HBV infection. About 50 percent of the population have been infected with HBV, and about 812 percent of the population, that is, more than 100m people, are carriers of hepatitis B surface antigen. About 1 million people die each year from acute and chronic HBV infections. Currently, interferon and adenosine analogues are approved by FDA, and there are only a few drugs that inhibit HBV replication, but their effects are limited. Adenosine analogues such as lamivudine and adefovir dipivoxil act by inhibiting the reverse transcription activity of HBV, which directly affects viral replication. Although these drugs can effectively eliminate HBV DNA in serum, they can not completely eliminate HBV infection in vivo. Therefore, HBV will recur after stopping treatment, and the prolongation of medication time will lead to the production of HBV virus mutants. RNA interference RNAi technique is an endogenous or exogenous double-stranded RNA-dsRNA-mediated mRNA degradation in cells, resulting in silencing of target gene expression, resulting in the loss of functional phenotypes. This phenomenon belongs to posttranscriptional gene silencing mechanism. RNAi activity in mammalian cells is mainly achieved by 21~23nt long small interfering RN AssiRNAs. Studies have shown that siRNA has been shown to scavenge the target gene in many fields, so siRNA has become an important alternative in the treatment of HBV infection. Since February 1998, when two scientists, Fire and Mello, first published on Nature: injecting dsRNA into a nematode, Caenorhabditis elegant anss, the dsRNA has induced gene targeting to specific gene expression, silent gene silencing, and so on. Many researchers have used RNAi technology to do a lot of research in online insects, fruit flies, plants, animal eggs and mammalian cells.
【學(xué)位授予單位】：第一軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R346;Q789

【共引文獻】

相關(guān)期刊論文 前1條

1 Robert R.Granados;G.W.Blissard1;;Insect Cell Culture and Biotechnology[J];Virologica Sinica;2007年02期

本文編號：1882906