Anti-HCV RNA Aptamers Targeting the Genomic cis-Acting Replication Element

Marton, Soledad; Berzal-Herranz, Beatriz; Garmendia, Eva; Cueto, Francisco J.; Berzal‐Herranz, Alfredo

doi:10.3390/ph5010049

Cited by 13 publications

(23 citation statements)

References 36 publications

(50 reference statements)

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“…They also provide an interesting means of developing molecular tools for deciphering the functional role of genomic structural elements, and therefore the identification of potential therapeutic targets. This has already been shown for other, closely related viruses such as HCV (Marton et al, 2011, 2013; Fernández-Sanlés et al, 2015) as well as non-related viruses such as HIV (Sánchez-Luque et al, 2014). Aptamers can be chemically modified quite easily to increase their stability and improve their efficiency.…”

Section: Nucleic Acids Targeting Flavivirus Genomessupporting

confidence: 58%

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

et al. 2017

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The genus Flavivirus comprises a large number of small, positive-sense single-stranded, RNA viruses able to replicate in the cytoplasm of certain arthropod and/or vertebrate host cells. The genus, which has some 70 member species, includes a number of emerging and re-emerging pathogens responsible for outbreaks of human disease around the world, such as the West Nile, dengue, Zika, yellow fever, Japanese encephalitis, St. Louis encephalitis, and tick-borne encephalitis viruses. Like other RNA viruses, flaviviruses have a compact RNA genome that efficiently stores all the information required for the completion of the infectious cycle. The efficiency of this storage system is attributable to supracoding elements, i.e., discrete, structural units with essential functions. This information storage system overlaps and complements the protein coding sequence and is highly conserved across the genus. It therefore offers interesting potential targets for novel therapeutic strategies. This review summarizes our knowledge of the features of flavivirus genome functional RNA domains. It also provides a brief overview of the main achievements reported in the design of antiviral nucleic acid-based drugs targeting functional genomic RNA elements.

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Section: Nucleic Acids Targeting Flavivirus Genomessupporting

confidence: 58%

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

et al. 2017

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“…To identify RNA molecules that specifically bind and possibly interfere with the activity of the CRE located at the 3′ end of the NS5B coding region [11], a SELEX procedure [37] was performed in which the target was a 194‐nt‐long RNA fragment (HCV‐CRE 194 ) of the HCV‐1b Con1 genome [29]. The target fragment spanned from nucleotide 9181–9371 and included the essential domains 5BSL3.1, 5BSL3.2 and 5BSL3.3 that make up the CRE element (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Hepatitis C virus‐CRE 194 RNA was obtained by in vitro transcription of the Sal I‐linearized plasmid construct pUC18‐T7HCV9181‐9371, as previously described [29]. The 3′HCV9181 RNA used in in vitro NS5B‐binding assays was obtained as described elsewhere [16].…”

Section: Methodsmentioning

confidence: 99%

RNA aptamer‐mediated interference of HCV replication by targeting the CRE‐5BSL3.2 domain

Marton¹,

Romero-López²,

Berzal‐Herranz³

2012

Journal of Viral Hepatitis

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Summary. The RNA genome of hepatitis C virus (HCV) contains multiple conserved structural RNA domains that play key roles in essential viral processes. A conserved structural component within the 3′ end of the region coding for viral RNA‐dependent RNA polymerase (NS5B) has been characterized as a functional cis‐acting replication element (CRE). This study reports the ability of two RNA aptamers, P‐58 and P‐78, to interfere with HCV replication by targeting the essential 5BSL3.2 domain within this CRE. Structure‐probing assays showed the binding of the aptamers to the CRE results in a structural reorganization of the apical portion of the 5BSL3.2 stem‐loop domain. This interfered with the binding of the NS5B protein to the CRE and induced a significant reduction in HCV replication (≈50%) in an autonomous subgenomic HCV replication system. These results highlight the potential of this CRE as a target for the development of anti‐HCV therapies and underscore the potential of antiviral agents based on RNA aptamer molecules.

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“…Interestingly, a RNA aptamer, named AP30, was able to recognize this minus-IRES region and reduce positive-strand genomic RNA synthesis [96]. To inhibit HCV replication, Marton et al selected RNA aptamers against CRE element that were able to repress replication of HCV replicon in hepatic cells [98]. Subsequently, two selected aptamers, P58 and P78, interact with subdomain 5BSL3.2 of the CRE element and produce a structural reorganization of the 3′ end HCV genome and a significant decrease of HCV replication in vivo [99].…”

Section: Aptamers For Virus Diagnosis and Treatmentmentioning

confidence: 99%

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

González

Martı́n

Fernández³

et al. 2016

Pharmaceuticals

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Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment.

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Anti-HCV RNA Aptamers Targeting the Genomic cis-Acting Replication Element

Cited by 13 publications

References 36 publications

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes

RNA aptamer‐mediated interference of HCV replication by targeting the CRE‐5BSL3.2 domain

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

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