Specific inhibition of HIV-1 gene expression by double-stranded RNA

Park, Wee-Sung; Miyano-Kurosaki, Naoko; Nakajima, Emiko; Takaku, Hiroshi

doi:10.1093/nass/1.1.219

Cited by 4 publications

(4 citation statements)

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“…The ability to stably express siRNA/shRNA using viral vectors renders the possibility of using RNAi as a form of gene therapy to specifically inhibit viral infection. Previously reports have shown that RNAi can be used to successfully downregulate the expression of a number of HIV‐1 genes including gag , pol , tat , vif , nef and rev , and reduce HIV‐1 infectivity [6–18]. However, the high mutation rate of HIV will lead to viral mutants that can escape from the inhibition of siRNAs targeting viral genes [19–21].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, RNAi‐mediated knockdown of cellular factors implicated in supporting the HIV‐1 life cycle offers an alternative approach to overcome this obstacle. In fact, cellular factors such as CD4, CXCR4, CCR5, NF‐kB, P‐TEFb, Cyclophilin A, DC‐SIGN, SPT‐5 and PARP‐1 have been successfully downregulated, resulting in the inhibition of HIV‐1 replication and infection [6,11,13,15,16,22–32]. However, whether downregulation of cellular genes can result in apoptotic cell death has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Specific inhibition of HIV‐1 replication by short hairpin RNAs targeting human cyclin T1 without inducing apoptosis

Li¹,

Xiong²,

Peng³

et al. 2005

FEBS Letters

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RNA interference (RNAi), a sequence-specific RNA degradation mechanism mediated by small interfering RNA (siRNA), can be used not only as a research tool but also as a therapeutic strategy for viral infection. We demonstrated that intracellular expression of short hairpin RNA (shRNA) targeting human cyclin T1 (hCycT1), a cellular factor essential for transcription of messenger and genomic RNAs from the long terminal repeat promoter of provirus of human immunodeficiency virus type 1 (HIV-1), could effectively suppress the replication of HIV-1. We also showed that downregulation of hCycT1 did not cause apoptotic cell death, therefore, targeting cellular factor hCycT1 by shRNAs may provide an attractive approach for genetic therapy of HIV-1 infection in the future.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Specific inhibition of HIV‐1 replication by short hairpin RNAs targeting human cyclin T1 without inducing apoptosis

Li¹,

Xiong²,

Peng³

et al. 2005

FEBS Letters

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“…Silencing these receptors is also a suitable strategy to prevent the host from virus entry. The si-RNAs were delivered prior to HIV-1 infection either by transfection [168,169] or using a lentiviral vector [170]. A similar phenomenon was observed when targeting the human chemokine receptor protein CCR5, which is a necessary co-receptor for infection by most strains of HIV-1.…”

Section: Rna Interferencementioning

confidence: 80%

Drugs Made of RNA: Development and Application of Engineered RNAs for Gene Therapy

Drude¹,

Dombos²,

Vauléon

et al. 2007

MRMC

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During the past decade, RNA has become a focus of investigation into new therapeutic schemes: antisense RNA, interfering RNA and trans-cleaving ribozymes are used to silence undesired gene expression. As an additional option with its own therapeutic potential, ribozymes may be employed to specifically alter the sequence of RNA. Among these RNA based strategies the mode of action varies: while antisense and interfering RNAs are capable of making specific contacts to other RNA molecules with the result of employing the cellular machinery for degradation of the RNA target, trans-cleaving ribozymes fold into specific three-dimensional structures to form catalytic centres and to specifically cleave a chosen RNA target. Beyond this, trans-splicing ribozymes have been engineered to first cleave a RNA target followed by ligation of a new RNA fragment delivered with the ribozyme. The latter strategy potentially extends the application of ribozymes from inhibition of gene expression to RNA repair, i. e. correction of genetic disorders at the level of RNA, and has already shown promising results in cell culture experiments. On the other side, advances in RNA synthesis, ribozyme engineering, delivery methods and expression systems have greatly enhanced the prospects of ribozymes, antisense and interfering RNAs in gene therapy. This review provides an overview of existing strategies for potential RNA based gene therapy. It is focussed on the engineering of ribozymes and functional RNAs to be used as drugs and on the basic molecular principles of their action.

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“…siRNA directed against hCycT1 could effectively suppress HIV‐1 replication without any induction of apoptotic cell death 48. In previous studies, downregulation of other cellular factors, such as CD4, CXCR4, CCR5, NF‐kB, P‐TEFb, cyclophilin A, DC‐SIGN, SPT‐5 and PARP‐1, successfully inhibited HIV‐1 replication 49–64. However, since many of these molecules are essential for cellular processes (CD4, e.g., is a cell‐surface molecule important for adaptive immune response), not all of them can serve as a practical target for HIV gene therapy.…”

Section: Inhibition Of Viral Infection By Rnaimentioning

confidence: 99%

RNA interference for antiviral therapy

Ketzinel-Gilad¹,

Shaul

Galun³

2006

The Journal of Gene Medicine

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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.

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Specific inhibition of HIV-1 gene expression by double-stranded RNA

Cited by 4 publications

References 0 publications

Specific inhibition of HIV‐1 replication by short hairpin RNAs targeting human cyclin T1 without inducing apoptosis

Specific inhibition of HIV‐1 replication by short hairpin RNAs targeting human cyclin T1 without inducing apoptosis

Drugs Made of RNA: Development and Application of Engineered RNAs for Gene Therapy

RNA interference for antiviral therapy

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