Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference

Park, W.-S.

doi:10.1093/nar/gkf627

Cited by 113 publications

(62 citation statements)

References 36 publications

(11 reference statements)

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“…Therefore, the use of synthetic siRNAs provides a rapid and cost-effective tool for new anti-HIV-1 gene therapeutics. 19 The ability of siRNA to control ischemia reperfusion injury related transcription factors, apoptosis, oxidative stress molecules, and complement factors supports the observation that RNAi-based therapeutics epitomize a novel and promising strategy for the control of IRI. 20 …”

Section: Resultsmentioning

confidence: 82%

An in silico approach to design potential siRNA molecules for ICP22 (US1) gene silencing of different strains of human herpes simplex 1

Nur¹,

Amin²,

Alam³

et al. 2013

Journal of Young Pharmacists

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a b s t r a c tBackground: The herpes simplex virus (HSV-1) is a virus that manifests itself in viral infection with painful, watery blisters in the skin or on the genitals as well as mucous membrane such as the mouth or lips. During an outbreak, the disease is contagious particularly and is irredeemable with present technology. Genetic studies of HSV-1 have shown that ICP22 (US1) gene is an immediate early gene and is responsible for genome replication and also has contribution in viral infection. Method: For disease diagnosis, ICP22 (US1) gene may be suitable target. Viral activity can be controlled through RNA interference technology, a significant method for the post-transcriptional gene silencing. However, in different viral isolates there is a genetic variability; it is very challenging to design possible siRNA molecules which can silence the respective target genes. The work was done by using various computational tools as similarity search, target alignment, secondary structure prediction and RNA interaction evaluation. Result: In our study two effective siRNA molecules for ICP22 (US1) gene silencing of seven different strains of HSV-1 were rationally designed and authenticated using computational methods, which might lead to knockdown the viral activity. Conclusion: siRNA molecules were foreseen against ICP22 (US1) gene of different strains of HSV-1 as effective aspirant using computational methods. Thus, the approach may deliver a vision for the chemical synthesis of antiviral RNA molecule for treatment of HSV-1, at genomic level.

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Section: Resultsmentioning

confidence: 82%

An in silico approach to design potential siRNA molecules for ICP22 (US1) gene silencing of different strains of human herpes simplex 1

Nur¹,

Amin²,

Alam³

et al. 2013

Journal of Young Pharmacists

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“…70,71 Additionally, RNAi-based therapies have been investigated for the treatment of human immunodeficiency virus (HIV) infection. Several early and late HIV-encoded RNAs including the TAR element, 84 tat, 50,85,86 rev, 50,85 gag, 87,88 env, 88 vif, 84 nef 84 and reverse transcriptase, 86 have been targeted by short RNAs in various cell lines and primary hematopoietic cells. A recent study has demonstrated sustained siRNA-mediated inhibition of HIV type 1 in terminally differentiated macrophages, which constitute an important reservoir of HIV in vivo.…”

Section: Potential Clinical Applications Of Short Rnasmentioning

confidence: 99%

RNA interference and potential therapeutic applications of short interfering RNAs

2005

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RNA interference is an endogenous gene-silencing mechanism that involves double-stranded RNA-mediated sequence-specific mRNA degradation. The discovery of this pathway together with the elucidation of the structure and function of short interfering RNAs -the effector molecules of RNA interference -has had an enormous impact on experimental biology. RNA interference technologies are currently the most widely utilized techniques in functional genomic studies. Furthermore, there is an intense research effort aimed at developing short interfering RNAs for therapeutic purposes. A number of proof-of-principle experiments have demonstrated the clinical potential of appropriately designed short interfering RNAs in various diseases including viral infections, cancer and neurodegenerative disorders. Already, in such a short time from their discovery, Acuity Pharmaceuticals (August 2004) and Sirna Therapeutics (September 2004) have filed Investigational New Drug applications with the US FDA to begin clinical trials with modified siRNA molecules in patients with age-related macular degeneration. This review will give a brief overview of the mechanism of RNA interference and applications of the pathway in experimental biology will be discussed. The article will focus on recent developments related to the use of RNA interference technologies in mammalian systems and on potential clinical applications of short interfering RNA-mediated RNA interference.

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“…HIV-1-specific siRNAs can inhibit infection in permanent cell lines, primary CD4 + T-cells and macrophages (Song et al, 2003). An event in the viral life cycle is inhibited after fusion and before reverse transcription (RT) (Brummelkamp et al, 2002), which has a crucial role in the processing of premature RNA and H1 (Myslinski et al, 2001) (Paddison et al, 2002;Paul et al, 2002;Sui et al, 2002), or the sense and antisense (tandem type) strands can be transcribed from two different pol III promoters in the same vector (Park et al, 2002). Furthermore, the siRNA duplexes are more potent inhibitors than the antisense RNAs.…”

Section: Hiv-1 Infection Is a Worldwide Disease That Requires Alternamentioning

confidence: 99%

Silencing of HIV-1 Gene Expression by Two Types of siRNA Expression Systems

Hayafune

Miyano-Kurosaki

Park

et al. 2006

Antivir Chem Chemother

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The RNA interference (RNAi) phenomenon is a recently discovered process in which the introduction of a double-stranded RNA (dsRNA) into cells causes the specific degradation of mRNA containing the same sequence. We designed mammalian expression vectors that direct the synthesis of small interfering RNA (siRNA)-like transcripts and examined them for their siRNAmediated gene interference targeting the env gene (NL4-3:7490-7508, E7490). We constructed siRNA expression vectors for two different strands (sense and antisense; tandem promoter) and for siRNA expressed from the short hairpin RNA (shRNA). The inhibition efficacy on HIV-1 replication differed between these two vectors. Notably, the shRNA vector pU6-env-shRNA inhibited p24 production more effectively than the tandem promoter expression vector pU6-env-siRNA. Furthermore, we examined the ability of lentiviral vectors expressing shRNA to suppress HIV-1 expression in HIV-1-infected SupT1 cells. The envshRNA (E 7490) almost completely suppressed HIV-1 expression in infected cells for up to 15 days.

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Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference

Cited by 113 publications

References 36 publications

An in silico approach to design potential siRNA molecules for ICP22 (US1) gene silencing of different strains of human herpes simplex 1

An in silico approach to design potential siRNA molecules for ICP22 (US1) gene silencing of different strains of human herpes simplex 1

RNA interference and potential therapeutic applications of short interfering RNAs

Silencing of HIV-1 Gene Expression by Two Types of siRNA Expression Systems

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