Selective inhibition of hepatitis B virus replication by RNA interference

Ying, Chunxiao; Clercq, Erik De; Neyts, Johan

doi:10.1016/j.bbrc.2003.08.021

Cited by 80 publications

(43 citation statements)

References 9 publications

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“…Plasmid DNA containing the JCV genome was used to generate a standard curve against which the samples were analyzed using iCycler software (Bio-Rad). In this respect, the use of RNA interference, which prevents the expression of genes by the use of small molecules, such as siRNAs, has recently received special attention due to its ability to affect viral gene expression (3,11,14,27). Once formed, siRNAs can be incorporated into a protein complex that recognizes and cleaves target mRNAs (10).…”

Section: Vol 78 2004 Notes 7265mentioning

confidence: 99%

Intracellular Approach for Blocking JC Virus Gene Expression by Using RNA Interference during Viral Infection

Radhakrishnan

Gordon

Valle

et al. 2004

J Virol

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Section: Vol 78 2004 Notes 7265mentioning

confidence: 99%

Intracellular Approach for Blocking JC Virus Gene Expression by Using RNA Interference during Viral Infection

Radhakrishnan

Gordon

Valle

et al. 2004

J Virol

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“…Efficacy of surface ORF-targeted siRNAs was reported in other studies [69,70] . Improved knockdown by repeated siRNA transfection of cells in culture was also observed [71] as well as effectiveness against a HBV target that includes the sequences encoding the lamivudine-resistance YMDD polymerase gene mutation [72] . Recently, Morrissey and colleagues showed that chemically modified siRNAs caused potent and persistent anti-HBV activity in vivo [73] .…”

Section: Hbvmentioning

confidence: 89%

Harnessing the RNA interference pathway to advance treatment and prevention of hepatocellular carcinoma

Arbuthnot

Thompson²

2008

WJG

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INTRODUCTIONGlobally, hepatocellular carcinoma (HCC) is a major cause of mortality [1,2] . It is the commonest primary liver cancer and accounts for 80%-90% of this class of malignancy. HCC is characterized by a very poor prognosis and is associated with high mortality. Annual mortality from HCC is virtually the same as its annual incidence, attesting to its rapid course and grave prognosis. Moreover, although HCC is the fifth most common cancer worldwide, it is the third most common cause of cancer-related mortality [3] . Recent observations have shown that incidence and mortality from liver cancer in the United States is the fastest growing of all cancers [2] . This is despite a decline in the overall cancer mortality rate that has occurred during the past 20 years. Currently available treatments of HCC are largely inadequate. However, with better understanding of the molecular pathogenesis of the cancer and significant advances in gene silencing technology, improved approaches are being devised to counter the malignancy. In particular, harnessing the RNA interference (RNAi) pathway to inhibit expression of genes that are implicated in transformation of hepatocytes is an exciting new approach to treating HCC. Therapeutic gene silencing technology is however at an early stage of development and there are several important hurdles that need to be overcome before this approach becomes a reality for treating HCC. In this review, we summarize HCC molecular pathogenesis as a background to discussing the interesting prospects of RNAi-based drugs for treating HCC. CaUses aND mOleCUlaR paThOgeNesIs Of hCCThere are several etiological agents and risk factors that AbstractPrimary liver cancer is the fifth most common malignancy in the world and is a leading cause of cancer-related mortality. Available treatment for hepatocellular carcinoma (HCC), the commonest primary liver cancer, is rarely curative and there is a need to develop therapy that is more effective. Specific and powerful gene silencing that can be achieved by activating RNA interference (RNAi) has generated enthusiasm for exploiting this pathway for HCC therapy. Many studies have been carried out with the aim of silencing HCC-related cellular oncogenes or the hepatocarcinogenic hepatitis B virus (HBV) and hepatitis C virus (HCV). Proof of principle studies have demonstrated promising results, and an early clinical trial assessing RNAi-based HBV therapy is currently in progress. Although the data augur well, there are several significant hurdles that need to be overcome before the goal of RNAi-based therapy for HCC is realized. Particularly important are the efficient and safe delivery of RNAi effectors to target malignant tissue and the limitation of unintended harmful non-specific effects.

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“…Several groups have reported using siRNAs to inhibit HBV replication in cell cultures and animal models [12][13][14][15][16][17][18][19] . Although all of these reports showed that HBV replication was inhibited to various degrees by siRNAs, several factors must be taken into account before siRNAs are used to treat HBV infection.…”

Section: Discussionmentioning

confidence: 99%

“…The physiological functions of RNAi are not very clear as yet, but it has been used successively as a potent method of gene knockdown in study of gene function and in experimental treatment of some diseases [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . In mammalian cells, double-stranded RNAs inducing RNAi must be short in length (<30 bp) so that they would not activate nonspecific interferon reactions.…”

Section: Introductionmentioning

confidence: 99%

Effect of vector-expressed siRNA on HBV replication in hepatoblastoma cells

Liu

Guo²,

Xue³

et al. 2004

WJG

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AIM:To study the effect of siRNA expressed from DNA vector on HBV replication. METHODS:Human U6 promoter was amplified from genomic DNA and cloned into plasmid pUC18 to construct a mammalian siRNA expression vector pUC18U6. Then oligonucleotides coding for a short hairpin RNA against HBV were cloned into pUC18U6 to form pUC18U6HBVsir which was introduced into 2.2.15 cells by using liposome-mediated transfection. 2.2.15 cells transfected by pUC18U6 and pUC18U6GFPsir which expressed siRNA against green fluorescent protein and mock-transfected 2.2.15 cells were used as controls. Concentration of HBsAg in the supernatant of the transfected cells was measured by using solid-phase radioimmunoassay. RESULTS:A mammalian siRNA expression vector pUC18U6 was constructed successfully. Compared with controls, pUC18U6HBVsir which expressed siRNA against HBV decreased concentration of HBsAg significantly by 44%(P<0.05).CONCLUSION: HBV replication in 2.2.15 cells is inhibited by siRNA expressed from the DNA vector.

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Selective inhibition of hepatitis B virus replication by RNA interference

Cited by 80 publications

References 9 publications

Intracellular Approach for Blocking JC Virus Gene Expression by Using RNA Interference during Viral Infection

Intracellular Approach for Blocking JC Virus Gene Expression by Using RNA Interference during Viral Infection

Harnessing the RNA interference pathway to advance treatment and prevention of hepatocellular carcinoma

Effect of vector-expressed siRNA on HBV replication in hepatoblastoma cells

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