RNA interference and its therapeutic potential

AbstractRNA interference is a technique that has become popular in the past few years. This is a biological method to detect the activity of a specific gene within a cell. RNAi is the introduction of homologous double stranded RNA to specifically target a gene’s product resulting in null or hypomorphic phenotypes. This technique involves the degradation of specific mRNA by using small interfering RNA. Both microRNA (miRNA) and small interfering RNA (siRNA) are directly related to RNA interference. RNAi mechanism is being explored as a new technique for suppressing gene expression. It is an important issue in the treatment of various diseases. This review considers different aspects of RNAi technique including its history of discovery, molecular mechanism, gene expression study, advantages of this technique against previously used techniques, barrier associated with this technique, and its therapeutic application.

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Antiviral Effects of Small Interfering RNA Simultaneously Inducing RNA Interference and Type 1 Interferon in Coxsackievirus Myocarditis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06050-12 ◽

2012 ◽

Vol 56 (7) ◽

pp. 3516-3523 ◽

Cited By ~ 5

Author(s):

Jeonghyun Ahn ◽

Ara Ko ◽

Eun Jung Jun ◽

Minah Won ◽

Yoo Kyum Kim ◽

...

Keyword(s):

Rna Interference ◽

Small Interfering Rna ◽

Antiviral Treatment ◽

Coxsackievirus B3 ◽

Hydroxyl Group ◽

Specific Gene ◽

Type I ◽

Antiviral Effects ◽

Direct Demonstration ◽

Interfering Rna

ABSTRACTAntiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5′-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5′ end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases.

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Small Interfering RNA–Mediated Suppression of Fas Modulate Apoptosis and Proliferation in Rat Intervertebral Disc Cells

Asian Spine Journal ◽

10.4184/asj.2017.11.5.686 ◽

2017 ◽

Vol 11 (5) ◽

pp. 686-693

Author(s):

Jong-Beom Park ◽

Chanjoo Park

Keyword(s):

Gene Expression ◽

Mammalian Cells ◽

Small Interfering Rna ◽

Mrna Level ◽

Serum Deprivation ◽

Specific Gene ◽

Disc Cells ◽

Fetal Bovine ◽

Interfering Rna

<sec><title>Study Design</title><italic>In vitro</italic> cell culture model.</sec><sec><title>Purpose</title>To investigate the effect of small interfering RNA (siRNA) on Fas expression, apoptosis, and proliferation in serum-deprived rat disc cells.</sec><sec><title>Overview of Literature</title>Synthetic siRNA can trigger an RNA interference (RNAi) response in mammalian cells and precipitate the inhibition of specific gene expression. However, the potential utility of siRNA technology in downregulation of specific genes associated with disc cell apoptosis remains unclear.</sec><sec><title>Methods</title>Rat disc cells were isolated and cultured in the presence of either 10% fetal bovine serum (FBS) (normal control) or 0% FBS (serum deprivation to induce apoptosis) for 48 hours. Fas expression, apoptosis, and proliferation were determined. Additionally, siRNA oligonucleotides against Fas (Fas siRNA) were transfected into rat disc cells to suppress Fas expression. Changes in Fas expression were assessed by reverse transcription-polymerase chain reaction and semiquantitatively analyzed using densitometry. The effect of Fas siRNA on apoptosis and proliferation of rat disc cells were also determined. Negative siRNA and transfection agent alone (Mock) were used as controls.</sec><sec><title>Results</title>Serum deprivation increased apoptosis by 40.3% (<italic>p</italic><0.001), decreased proliferation by 45.3% (<italic>p</italic><0.001), and upregulated Fas expression. Additionally, Fas siRNA suppressed Fas expression in serum-deprived cultures, with 68.5% reduction at the mRNA level compared to the control cultures (<italic>p</italic><0.001). Finally, Fas siRNA–mediated suppression of Fas expression significantly inhibited apoptosis by 9.3% and increased proliferation by 21% in serum-deprived cultures (<italic>p</italic><0.05 for both).</sec><sec><title>Conclusions</title>The observed dual positive effect of Fas siRNA might be a powerful therapeutic approach for disc degeneration by suppression of harmful gene expression.</sec>

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SiMiSnoRNA: Collection of siRNA, miRNA, and snoRNA database for RNA interference / SiMiSnoRNA: RNA Interferansı için siRNA, miRNA ve snoRNA veritabanında depolanan siRNA, miRNA, and snoRNA koleksiyonları

Turkish Journal of Biochemistry ◽

10.1515/tjb-2015-0044 ◽

2015 ◽

Vol 40 (6) ◽

Author(s):

Umesh Kalathiya ◽

Monikaben Padariya ◽

Maciej Baginski ◽

Chintankumar Padariya

Keyword(s):

Gene Expression ◽

Rna Interference ◽

Small Rna ◽

Regulation Of Gene Expression ◽

Specific Gene ◽

Sequence Information ◽

Rna Molecules ◽

Inhibit Gene Expression ◽

Considerable Impact ◽

Interfering Rna

AbstractObjective: The discovery of sequence specific gene silencing which occurs due to the presence of double- stranded RNAs has considerable impact on biology, revealing an unknown level of regulation of gene expression. This process is known as RNA interference (RNAi) or RNA silencing in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecule. Two types of small RNA molecules-small interfering RNA (siRNA) and microRNA (miRNA) are central to RNA interference. Therefore, SMethods: SResults: A flexible web-based search engine is developed to obtain fast access to specific small RNA sequence information.Conclusion: BLAST search analysis within S

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Faculty Opinions recommendation of DICER-LIKE 4 is required for RNA interference and produces the 21-nucleotide small interfering RNA component of the plant cell-to-cell silencing signal.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1029052.345437 ◽

2005 ◽

Author(s):

Andy Maule

Keyword(s):

Rna Interference ◽

Plant Cell ◽

Small Interfering Rna ◽

Interfering Rna

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Amphiphysin 1 Is Important for Actin Polymerization during Phagocytosis

Molecular Biology of the Cell ◽

10.1091/mbc.e07-04-0296 ◽

2007 ◽

Vol 18 (11) ◽

pp. 4669-4680 ◽

Cited By ~ 30

Author(s):

Hiroshi Yamada ◽

Emiko Ohashi ◽

Tadashi Abe ◽

Norihiro Kusumi ◽

Shun-AI Li ◽

...

Keyword(s):

Rna Interference ◽

Sertoli Cells ◽

Small Interfering Rna ◽

Actin Polymerization ◽

Actin Dynamics ◽

Polymerization Process ◽

Amphiphysin 1 ◽

Phagocytic Cups ◽

Interfering Rna ◽

Constitutively Active

Amphiphysin 1 is involved in clathrin-mediated endocytosis. In this study, we demonstrate that amphiphysin 1 is essential for cellular phagocytosis and that it is critical for actin polymerization. Phagocytosis in Sertoli cells was induced by stimulating phosphatidylserine receptors. This stimulation led to the formation of actin-rich structures, including ruffles, phagocytic cups, and phagosomes, all of which showed an accumulation of amphiphysin 1. Knocking out amphiphysin 1 by RNA interference in the cells resulted in the reduction of ruffle formation, actin polymerization, and phagocytosis. Phagocytosis was also drastically decreased in amph 1 (−/−) Sertoli cells. In addition, phosphatidylinositol-4,5-bisphosphate–induced actin polymerization was decreased in the knockout testis cytosol. The addition of recombinant amphiphysin 1 to the cytosol restored the polymerization process. Ruffle formation in small interfering RNA-treated cells was recovered by the expression of constitutively active Rac1, suggesting that amphiphysin 1 functions upstream of the protein. These findings support that amphiphysin 1 is important in the regulation of actin dynamics and that it is required for phagocytosis.

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Specific inhibition of gene expression using a stably integrated, inducible small‐interfering‐RNA vector

EMBO Reports ◽

10.1038/sj.embor.embor865 ◽

2003 ◽

Vol 4 (6) ◽

pp. 609-615 ◽

Cited By ~ 357

Author(s):

Marc van de Wetering ◽

Irma Oving ◽

Vanesa Muncan ◽

Menno Tjon Pon Fong ◽

Helen Brantjes ◽

...

Keyword(s):

Gene Expression ◽

Small Interfering Rna ◽

Specific Inhibition ◽

Interfering Rna

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DrosophilaoncogeneGas41is an RNA interference modulator that intersects heterochromatin and the small interfering RNA pathway

FEBS Journal ◽

10.1111/febs.13115 ◽

2014 ◽

Vol 282 (1) ◽

pp. 153-173 ◽

Cited By ~ 4

Author(s):

Sumit G. Gandhi ◽

Indira Bag ◽

Saswati Sengupta ◽

Manika Pal-Bhadra ◽

Utpal Bhadra

Keyword(s):

Rna Interference ◽

Small Interfering Rna ◽

Interfering Rna

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Epigenetic determination of a cell-specific gene expression program by ATF-2 and the histone variant macroH2A

The EMBO Journal ◽

10.1038/sj.emboj.7601364 ◽

2006 ◽

Vol 25 (20) ◽

pp. 4843-4853 ◽

Cited By ~ 60

Author(s):

Marios Agelopoulos ◽

Dimitris Thanos

Keyword(s):

Gene Expression ◽

Histone Variant ◽

Gene Expression Program ◽

Specific Gene ◽

Specific Gene Expression ◽

A Cell ◽

Expression Program

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RNA Interference of Human Papillomavirus Type 18 E6 and E7 Induces Senescence in HeLa Cells

Journal of Virology ◽

10.1128/jvi.77.10.6066-6069.2003 ◽

2003 ◽

Vol 77 (10) ◽

pp. 6066-6069 ◽

Cited By ~ 137

Author(s):

Allison H. S. Hall ◽

Kenneth A. Alexander

Keyword(s):

Cell Proliferation ◽

Human Papillomavirus ◽

Rna Interference ◽

Hela Cells ◽

Tumor Suppressors ◽

Small Interfering Rna ◽

Promote Cell Proliferation ◽

E6 And E7 ◽

Cellular Dna ◽

Interfering Rna

ABSTRACT The human papillomavirus oncoproteins E6 and E7 promote cell proliferation and contribute to carcinogenesis by interfering with the activities of cellular tumor suppressors. We used a small interfering RNA molecule targeting the E7 region of the bicistronic E6 and E7 mRNA to induce RNA interference, thereby reducing expression of E6 and E7 in HeLa cells. RNA interference of E6 and E7 also inhibited cellular DNA synthesis and induced morphological and biochemical changes characteristic of cellular senescence. These results demonstrate that reducing E6 and E7 expression is sufficient to cause HeLa cells to become senescent.

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