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Total 371 results found since Jan 2013.

Enzymatically synthesized 2'-fluoro-modified Dicer-substrate siRNA swarms against herpes simplex virus demonstrate enhanced antiviral efficacy and low cytotoxicity.
Abstract Chemical modifications of small interfering (si)RNAs are used to enhance their stability and potency, and to reduce possible off-target effects, including immunogenicity. We have earlier introduced highly effective antiviral siRNA swarms against herpes simplex virus (HSV), targeting 653 bp of the essential UL29 viral gene. Here, we report a method for enzymatic production and antiviral use of 2'-fluoro-modified siRNA swarms. Utilizing the RNA-dependent RNA polymerase from bacteriophage phi6, we produced 2'-F-siRNA swarms containing either all or a fraction of modified adenosine, cytidine or uridine residu...
Source: Antiviral Research - August 12, 2020 Category: Virology Authors: Levanova AA, Kalke KM, Lund LM, Sipari N, Sadeghi M, Nyman MC, Paavilainen H, Hukkanen V, Poranen MM Tags: Antiviral Res Source Type: research

Viruses, Vol. 12, Pages 1434: Herpes Simplex Virus Type 1 Clinical Isolates Respond to UL29-Targeted siRNA Swarm Treatment Independent of Their Acyclovir Sensitivity
Poranen Veijo Hukkanen Acyclovir is the drug of choice for the treatment of herpes simplex virus (HSV) infections. Acyclovir-resistant HSV strains may emerge, especially during long-term drug use, and subsequently cause difficult-to-treat exacerbations. Previously, we set up a novel treatment approach, based on enzymatically synthesized pools of siRNAs, or siRNA swarms. These swarms can cover kilobases-long target sequences, reducing the likelihood of resistance to treatment. Swarms targeting the UL29 essential gene of HSV-1 have demonstrated high efficacy against HSV-1 in vitro and in vivo. Here, we assessed the an...
Source: Viruses - December 13, 2020 Category: Virology Authors: Kiira Kalke Jenni Lehtinen Jelena Gnjatovic Liisa M. Lund Marie C. Nyman Henrik Paavilainen Julius Orpana Tuomas Lasanen Fanny Frejborg Alesia A. Levanova Tytti Vuorinen Minna M. Poranen Veijo Hukkanen Tags: Article Source Type: research

Antitumor activities of an oncolytic adenovirus equipped with a double siRNA targeting Ki67 and hTERT in renal cancer cells.
In this study, we constructed novel oncolytic adenoviruses in which the Ki67 core promoter drove expression of the E1A gene. These adenoviruses were equipped with either a Ki67 small interfering RNA (siRNA), a human telomerase reverse transcriptase (hTERT) siRNA or a double siRNA targeting Ki67 and hTERT. We identified the antitumor activities of oncolytic adenoviruses in 3 renal cancer cell lines, human normal renal tube cell HK-2 and also in nude mice bearing KETR-3-xenografted tumors. Our results showed that these oncolytic adenoviruses, especially Ki67-ZXC2-double siRNA, could effectively induce silencing of the Ki67 a...
Source: Virus Research - January 21, 2014 Category: Virology Authors: Fang L, Cheng Q, Li W, Liu J, Li L, Xu K, Zheng J Tags: Virus Res Source Type: research

Kinome siRNA screen identifies novel cell-type specific dengue host target genes.
Abstract Dengue is a global emerging infectious disease, with no specific treatment available. To identify novel human host cell targets important for dengue virus infection and replication, an image-based high-throughput siRNA assay screening of a human kinome siRNA library was conducted using human hepatocyte cell line Huh7 infected with a recent dengue serotype 2 virus isolate BR DEN2 01-01. In the primary siRNA screening of 779 kinase-related genes, knockdown of 22 genes showed a reduction in DENV-2 infection. Conversely, knockdown of 8 genes enhanced viral infection. To assess host cell specificity, the confi...
Source: Antiviral Research - July 18, 2014 Category: Virology Authors: Kwon YJ, Heo J, Wong HE, Cruz DJ, Velumani S, da Silva CT, Mosimann AL, Duarte Dos Santos CN, Freitas-Junior LH, Fink K Tags: Antiviral Res Source Type: research

Combination of specific single chain antibody variable fragment and siRNA has a synergistic inhibitory effect on the propagation of avian influenza virus H5N1 in chicken cells
Conclusions: A novel combination of antiviral siRNAs expressed in chicken cells and chicken antibody single-chain variable fragments (scFvs) secreted from the cells has a synergistic inhibitory effect on the avian influenza viral proliferation in vitro. Intracellular application of scFvs and anti-viral siRNA may provide a new approach to influenza prevention and treatment.
Source: Virology Journal - November 29, 2014 Category: Virology Authors: Shuang WangPeng ZhangFei HeJi-Gui WangJia-Zeng SunZhi-Li LiBao YiJi XiYa-Ping MaoQiang HouDao-Li YuanZi-Ding ZhangWei-Quan Liu Source Type: research

Inhibition of clinical pathogenic herpes simplex virus 1 strains with enzymatically created siRNA pools
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Source: Journal of Medical Virology - May 19, 2016 Category: Virology Authors: Henrik Paavilainen, Jenni Lehtinen, Alesia Romanovskaya, Michaela Nygårdas, Dennis H. Bamford, Minna M. Poranen, Veijo Hukkanen Tags: Research Article Source Type: research

High-degree and broad-spectrum resistance mediated by a combination of NIb siRNA and miRNA suppresses replication of necrotic and common strains of potato virus Y
In this study, we designed specific siRNAs and miRNAs to target two regions of the PVYO replicase gene (NIb). Eight plant expression vectors containing one or two sRNAs were constructed. Luciferase activity assays showed that the designed sRNAs successfully cleaved theNIb gene of PVYO and PVYN, and the vector carrying a combined siRNA- and miRNA-based short hairpin RNA (shRNA) demonstrated the strongest inhibitory effect. These effects were confirmed through the acquisition of PVYO and PVYN resistance in transgenic sRNA-expressingNicotiana tabacum plants. This phenomenon could be related to a plant defense mechanism in whi...
Source: Archives of Virology - August 10, 2018 Category: Virology Source Type: research

Characterization of viral siRNA populations in honey bee colony collapse disorder.
Abstract Colony Collapse Disorder (CCD), a special case of collapse of honey bee colonies, has resulted in significant losses for beekeepers. CCD-colonies show abundance of pathogens which suggests that they have a weakened immune system. Since honey bee viruses are major players in colony collapse and given the important role of viral RNA interference (RNAi) in combating viral infections we investigated if CCD-colonies elicit an RNAi response. Deep-sequencing analysis of samples from CCD-colonies from US and Israel revealed abundant small interfering RNAs (siRNA) of 21-22 nucleotides perfectly matching the Israel...
Source: Virology - April 1, 2014 Category: Virology Authors: Chejanovsky N, Ophir R, Schwager MS, Slabezki Y, Grossman S, Cox-Foster D Tags: Virology Source Type: research

Pathogenesis of Soybean mosaic virus in soybean carrying Rsv1 gene is associated with miRNA and siRNA pathways, and breakdown of AGO1 homeostasis.
Abstract Profiling small RNAs in soybean Williams 82 (rsv), susceptible to Soybean mosaic virus (SMV, the genus Potyvirus, family Potyviridae) strains G2 and G7, and soybean PI96983 (Rsv1), resistant to G2 but susceptible to G7, identified the microRNA miR168 that was highly overexpressed only in G7-infected PI96983 showing a lethal systemic hypersensitive response (LSHR). Overexpression of miR168 was in parallel with the high-level expression of AGO1 mRNA, high-level accumulation of miR168-mediated AGO1 mRNA cleavage products but with severely repressed AGO1 protein. In contrast, AGO1 mRNA, degradation products a...
Source: Virology - January 12, 2015 Category: Virology Authors: Chen H, Zhang L, Yu K, Wang A Tags: Virology Source Type: research

Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different Influenza A virus strains of avian and swine origin.
In conclusion, these findings reveal new siRNA sequences able to inhibit Influenza A virus replication and provide a basis for the development of siRNAs as prophylaxis and therapy for influenza infection both in humans and animals. PMID: 25986248 [PubMed - as supplied by publisher]
Source: Antiviral Research - May 16, 2015 Category: Virology Authors: Stoppani E, Bassi I, Dotti S, Lizier M, Ferrari M, Lucchini F Tags: Antiviral Res Source Type: research

Mapping and identification of cassava mosaic geminivirus DNA-A and DNA-B genome sequences for efficient siRNA expression and RNAi based virus resistance by transient agro-infiltration studies.
In this study we made RNAi constructs for all the genes of both the genomic components (DNA-A and DNA-B) of African cassava mosaic virus (ACMV-CM), one of the most devastating geminiviruses causing cassava mosaic disease (CMD) in Africa. Using transient agro-infiltration studies, RNAi constructs were evaluated for their ability to trigger gene silencing against the invading virus and protection against it. The results show that the selection of the DNA target sequence is an important determinant for the amount of siRNA produced and the extent of resistance. The ACMV genes AC1, AC2, AC4from DNA-A and BC1 from DNA-B were eff...
Source: Virus Research - November 12, 2015 Category: Virology Authors: Patil BL, Bagewadi B, Yadav JS, Fauquet CM Tags: Virus Res Source Type: research

Viruses, Vol. 12, Pages 748: aBravo Is a Novel Aedes aegypti Antiviral Protein that Interacts with, but Acts Independently of, the Exogenous siRNA Pathway Effector Dicer 2
lain Kohl Mosquitoes, such as Aedes aegypti, can transmit arboviruses to humans. The exogenous short interfering RNA (exo-siRNA) pathway plays a major antiviral role in controlling virus infection in mosquito cells. The Dicer 2 (Dcr2) nuclease is a key effector protein in this pathway, which cleaves viral double-stranded RNA into virus-derived siRNAs that are further loaded onto an effector called Argonaute 2 (Ago2), which as part of the multiprotein RNA-induced silencing complex (RISC) targets and cleaves viral RNA. In order to better understand the effector protein Dcr2, proteomics experiments were conducted to ident...
Source: Viruses - July 10, 2020 Category: Virology Authors: Margus Varjak Rommel J. Gestuveo Richard Burchmore Esther Schnettler Alain Kohl Tags: Article Source Type: research

Viruses, Vol. 13, Pages 881: Rabies Prophylactic and Treatment Options: An In Vitro Study of siRNA- and Aptamer-Based Therapeutics
This study serves as a proof-of-concept to potentially use aptamers and siRNAs as rabies immunoglobulin (RIG) replacements or therapeutic options for RABV and provides strong evidence towards their further investigation.
Source: Viruses - May 11, 2021 Category: Virology Authors: Terence Peter Scott Louis Hendrik Nel Tags: Article Source Type: research

Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different Influenza A virus strains of avian and swine origin
In conclusion, these findings reveal new siRNA sequences able to inhibit Influenza A virus replication and provide a basis for the development of siRNAs as prophylaxis and therapy for influenza infection both in humans and animals.
Source: Antiviral Therapy - May 17, 2015 Category: Virology Source Type: research

Novel siRNA therapeutics demonstrate multi-variant efficacy against SARS-CoV-2
Antiviral Res. 2023 Jul 19:105677. doi: 10.1016/j.antiviral.2023.105677. Online ahead of print.ABSTRACTSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%. While global response strategies, which are predominantly reliant on regular vaccinations, have shifted from zero COVID to living with COVID, there is a distinct lack of broad-spectrum direct acting antiviral therapies that maintain efficacy across evolving SARS-CoV-2 variants of concern. This is of most concern for immunocompromised and immunosuppressed ...
Source: Antiviral Research - July 21, 2023 Category: Virology Authors: Ellen Bowden-Reid Scott Ledger Yuan Zhang Francesca Di Giallonardo Anupriya Aggarwal Alberto Ospina Stella Anouschka Akerman Vanessa Milogiannakis Gregory Walker William Rawlinson Stuart Turville Anthony D Kelleher Chantelle Ahlenstiel Source Type: research