Suppression of HIV-1 Replication by a Combination of Endonucleolytic Ribozymes (RNase P and tRNase ZL)

Ikeda, Masahiro; Habu, Yuichiro; Miyano-Kurosaki, Naoko; Takaku, Hiroshi

doi:10.1080/01457630600684120

Cited by 8 publications

(4 citation statements)

References 26 publications

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“…It has previously been shown that custom-designed EGS molecules could induce human RNase P to cleave HIV RNA sequence in vitro and could inhibit HIV infection in cultured cells [33], [34]. The approach described in the current study, which uses M1GS ribozymes for blocking HIV infection in human cells, is different from the EGS-based strategy.…”

Section: Discussionmentioning

confidence: 94%

“…Moreover, a reduction of 1000 fold in HSV-1 growth and a reduction of 150 fold in HCMV replication were observed in cells that expressed ribozymes derived from the wild type RNase P ribozyme sequence [30], [31]. It has previously been shown that custom-designed EGS molecules could induce human RNase P to cleave HIV RNA sequence in vitro and could inhibit HIV infection in cultured cells [33], [34]. However, it has not been reported whether M1GS ribozymes can block HIV infection in human cells.…”

Section: Introductionmentioning

confidence: 99%

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Effective Inhibition of Human Immunodeficiency Virus 1 Replication by Engineered RNase P Ribozyme

et al. 2012

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Using an in vitro selection procedure, we have previously isolated RNase P ribozyme variants that efficiently cleave an mRNA sequence in vitro. In this study, a variant was used to target the HIV RNA sequence in the tat region. The variant cleaved the tat RNA sequence in vitro about 20 times more efficiently than the wild type ribozyme. Our results provide the first direct evidence that combined mutations at nucleotide 83 and 340 of RNase P catalytic RNA from Escherichia coli (G83 -> U83 and G340 -> A340) increase the overall efficiency of the ribozyme in cleaving an HIV RNA sequence. Moreover, the variant is more effective in reducing HIV-1 p24 expression and intracellular viral RNA level in cells than the wild type ribozyme. A reduction of about 90% in viral RNA level and a reduction of 150 fold in viral growth were observed in cells that expressed the variant, while a reduction of less than 10% was observed in cells that either did not express the ribozyme or produced a catalytically inactive ribozyme mutant. Thus, engineered ribozyme variants are effective in inhibiting HIV infection. These results also demonstrate the potential of engineering RNase P ribozymes for anti-HIV application.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Effective Inhibition of Human Immunodeficiency Virus 1 Replication by Engineered RNase P Ribozyme

et al. 2012

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“…RNase P has also been studied as a powerful tool for targeted cleavage directed by external guide sequences [54]. The combination of RNase P and tRNase Z directed cleavage against the same target (HIV-1 RNA) in culture cells results in a more efficient suppression of the HIV-1 mRNA than the suppression obtained using only one of them [55].…”

Section: Model Substrates and Targeted Clea-vagementioning

confidence: 99%

tRNase Z

Ceballos¹,

Vioque²

2007

PPL

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Endonuclease tRNase Z catalyzes the generation of the mature 3' end of tRNA precursors through specific endonucleolytic cleavage. The enzyme has been characterized from organisms representative of all domains of life as well as from organelles, and the crystal structure of three bacterial enzymes has been determined. This review presents an overview of its properties and what is known about its structure, substrate recognition, cleavage site definition, and potential practical applications.

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“…32 In a follow-up study, a combination of RNAse P and RNAse Z L EGS were more efficient at reducing HIV-1 replication than EGS alone. 33 The efficacy of these anti-HIV EGS in long-term infectious assays awaits assessment.…”

Section: Ribozymes and Aptamers Continue To Evolve As Therapeuticsmentioning

confidence: 99%

Progress and prospects: RNA-based therapies for treatment of HIV infection

2007

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The current treatment regimen for HIV-infected individuals combines two or more drugs targeting different viral proteins such as RT and gag. Resistance to conventional drugs can develop quickly, and typically persists. The prospect of longer, continuous antiretroviral therapy brings with it the need for new antiretroviral drugs and approaches. In this context, gene therapies have the potential to prolong life and quality of life as an additional therapeutic class and may serve as an adjuvant to traditional treatments. This review focuses on RNA-based hematopoietic cell gene therapy for treatment of HIV infection. Recent advances in our understanding of RNA interference (RNAi) make this an especially attractive candidate for anti-HIV gene therapy although ribozyme and RNA decoy/aptamer approaches can be combined with RNAi to make a combinatorial therapy akin to highly active anti-retroviral therapy.

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Suppression of HIV-1 Replication by a Combination of Endonucleolytic Ribozymes (RNase P and tRNase ZL)

Cited by 8 publications

References 26 publications

Effective Inhibition of Human Immunodeficiency Virus 1 Replication by Engineered RNase P Ribozyme

Effective Inhibition of Human Immunodeficiency Virus 1 Replication by Engineered RNase P Ribozyme

tRNase Z

Progress and prospects: RNA-based therapies for treatment of HIV infection

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