Inhibition of HIV-1 reverse transcriptase by RNA aptamers in <i>Escherichia coli</i>

Nickens, David G.; Patterson, James T.; Burke, Donald H.

doi:10.1261/rna.5550103

Cited by 27 publications

(23 citation statements)

References 25 publications

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“…40,44 Numerous aptamers and RNA decoys have been selected to disrupt key stages of the viral life cycle including enzymatic function (by targeting reverse transcriptase (RT) and integrase), gene expression (targeted against Rev and Tat), viral packaging (targeted against nucleocapsid and p55 Gag proteins) and viral entry (targeted against gp120 and gp41) into the host cell (Figure 3). 36 As intracellularly expressed antiHIV-1 RT aptamers had shown promise as antiviral agents in cell culture assays, additional RT-directed aptamers continue to be described, including those that selectively inhibit the RNaseH domain of HIV-1 RT.…”

Section: Aptamers For Intracellular Targets Are Being Developedmentioning

confidence: 99%

Gene therapy progress and prospects: RNA aptamers

2007

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Aptamers are oligonucleotides evolved in vitro or in nature to bind target ligands with high affinity and specificity. They are emerging as powerful tools in the fields of therapeutics, drug development, target validation and diagnostics. Aptamers are attractive alternatives to antibody-and small-moleculebased therapeutics owing to their stability, low toxicity, low immunogenicity and improved safety. With the recent approval of the first aptamer drug Macugen by the US FDA, there is great impetus to develop therapeutic aptamers that can target a wide array of disease states. The recent demonstration that aptamer activity can be reversed by the administration of a simple antidote greatly enhances the potential value of aptamers as therapeutic agents.

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Section: Aptamers For Intracellular Targets Are Being Developedmentioning

confidence: 99%

Gene therapy progress and prospects: RNA aptamers

2007

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“…However, targets from relatively few viruses are represented. Examples include aptamers to HIV Tat and reverse transcriptase (Ye et al 1996;Nickens et al 2003), hepatitis C virus (HCV) polymerase (see Biroccio et al 2002;Vo et al 2003) and NS3 (Nishikawa et al 2003(Nishikawa et al , 2004, influenza hemagglutinin (Jeon et al 2004;Misono and Kumar 2005;Gopinath et al 2006), and bacteriophage MS2 coat protein Hirao et al 1998;Rowsell et al 1998;Shtatland et al 2000). In this article, we report the identification and characterization of the first aptamers to any protein from FMDV; the 3Dpol enzyme (serotype C).…”

Section: Introductionmentioning

confidence: 96%

Selection and characterization of RNA aptamers to the RNA-dependent RNA polymerase from foot-and-mouth disease virus

Ellingham¹,

Bunka²,

Rowlands³

et al. 2006

RNA

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Foot-and-mouth disease virus causes a highly contagious disease of agricultural livestock and is of enormous economic importance. Replication of the RNA genome of the virus, via negative strand intermediates, involves an RNA-dependent RNA polymerase (3Dpol). RNA aptamers specific to this enzyme have been selected and characterized. Some of these molecules inhibit enzymatic activity in vitro, with IC 50 values of <20 nM and K i values of 18-75 nM. Two of these show similarity, both with each other and with regions of the viral genome. Furthermore, truncated versions of one of the aptamers have been used to define the parts of the molecule responsible for its inhibitory activity.

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“…In stably transfected Tlymphoid cells, the pseudo-knot construct specifically reduced the replication capability of the virus [46]. In another study it was demonstrated that this pseudo-knot aptamer was also a potent reverse transcriptase inhibitor in bacterial cells [44]. Therefore, aptamers selected in vitro against a purified protein retain their binding efficacy on endogenous target and may modulate their biological function.…”

Section: Aptamers Targeting Proteinsmentioning

confidence: 99%

“…These results clearly demonstrated the correlation between the affinity and the inhibitory effect of the aptamers. Several aptamers directed against the reverse transcriptase had been previously demonstrated to be good inhibitors of the HIV-1 reverse transcription in vitro or in cultured cells [44][45][46]. The ''bifunctional aptamer'' strategy therefore extends the repertoire of potential targets for the design of antiviral molecules.…”

Section: Simultaneous Targetting Of Rna Hairpins In the Hiv-1mentioning

confidence: 99%

Regulating eukaryotic gene expression with aptamers

TOULME¹

2004

FEBS Letters

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Aptamers are RNA or DNA oligonucleotides identified within a randomly synthesized library, through an in vitro selection procedure. The selected candidates display a predetermined property of interest with respect to a given target. Successful selection has been carried out against targets ranging from small (amino acids, antibiotics) to macro-molecules (proteins, nucleic acids). They generally show an affinity in the nanomolar range and a high specificity of target recognition. Interestingly, aptamers selected against purified targets in the test tube retain their properties within cells. RNA aptamers can be generated in situ from an appropriate DNA construct or delivered as nuclease-resistant oligonucleotide analogues. For example, aptamers recognizing RNA structure through looploop interactions modulate the trans-activation of in vitro transcription mediated by the TAR RNA element of human immunodeficiency virus type 1. Consequently, they constitute both exquisite tools for functional genomics analysis and promising prototypes of therapeutic agents. Natural aptameric motifs have been identified within mRNA sequences, which upon binding to a metabolite control the expression of the encoded gene, which is generally involved in the biosynthesis of this particular metabolite.

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Inhibition of HIV-1 reverse transcriptase by RNA aptamers in Escherichia coli

Cited by 27 publications

References 25 publications

Gene therapy progress and prospects: RNA aptamers

Gene therapy progress and prospects: RNA aptamers

Selection and characterization of RNA aptamers to the RNA-dependent RNA polymerase from foot-and-mouth disease virus

Regulating eukaryotic gene expression with aptamers

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