Antagonistic RNA aptamer specific to a heterodimeric form of human interleukin-17A/F

Adachi, Hironori; Ishiguro, Akira; Hamada, Michiaki; Sakota, Eri; Asai, Kiyoshi; Nakamura, Yoshikazu

doi:10.1016/j.biochi.2011.04.003

Cited by 19 publications

(16 citation statements)

References 40 publications

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“…This is a unique situation and had not been previously observed when RNA aptamers were raised against the human interleukin-17A/F heterodimer [39]. This could be due to RNA aptamers forming more stable secondary and tertiary structures than ssDNA aptamers.…”

Section: Discussionmentioning

confidence: 82%

Selection and Application of ssDNA Aptamers to Detect Active TB from Sputum Samples

et al. 2012

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BackgroundDespite the enormous global burden of tuberculosis (TB), conventional approaches to diagnosis continue to rely on tests that have major drawbacks. The improvement of TB diagnostics relies, not only on good biomarkers, but also upon accurate detection methodologies. The 10-kDa culture filtrate protein (CFP-10) and the 6-kDa early secreted antigen target (ESAT-6) are potent T-cell antigens that are recognised by over 70% of TB patients. Aptamers, a novel sensitive and specific class of detection molecules, has hitherto, not been raised to these relatively TB-specific antigens.MethodsDNA aptamers that bind to the CFP-10.ESAT-6 heterodimer were isolated. To assess their affinity and specificity to the heterodimer, aptamers were screened using an enzyme-linked oligonucleotide assay (ELONA). One suitable aptamer was evaluated by ELONA using sputum samples obtained from 20 TB patients and 48 control patients (those with latent TB infection, symptomatic non TB patients, and healthy laboratory volunteers). Culture positivity for Mycobacterium tuberculosis (Mtb) served as the reference standard. Accuracy and cut-points were evaluated using ROC curve analysis.ResultsTwenty-four out of the 66 aptamers that were isolated bound significantly (p<0.05) to the CFP-10.ESAT-6 heterodimer and six were further evaluated. Their dissociation constant (KD) values were in the nanomolar range. One aptamer, designated CSIR 2.11, was evaluated using sputum samples. CSIR 2.11 had sensitivity and specificity of 100% and 68.75% using Youden’s index and 35% and 95%, respectively, using a rule-in cut-point.ConclusionThis preliminary proof-of-concept study suggests that a diagnosis of active TB using anti-CFP-10.ESAT-6 aptamers applied to human sputum samples is feasible.

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Section: Discussionmentioning

confidence: 82%

Selection and Application of ssDNA Aptamers to Detect Active TB from Sputum Samples

et al. 2012

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“…Aptamers are being tested for different purposes such as protein purification 18 or for protein-function regulation in an antagonistic or agonistic manner. 19,20,21 …”

Section: Discussionmentioning

confidence: 99%

Myelin Basic Protein and a Multiple Sclerosis-related MBP-peptide Bind to Oligonucleotides

Rozenblum

Kaufman

Vitullo

2014

Molecular Therapy - Nucleic Acids

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Aptamer ligands for myelin basic protein (MBP) were obtained using the systematic evolution of ligand by exponential enrichment (SELEX) method. Two clones were isolated from a pool of oligonucleotides and tested for MBP targeting. Using purified MBP, we demonstrated the binding activity of the aptamers and we also showed the affinity of MBP for oligonucleotides of specific length. Moreover, one selected aptamer competitively inhibited the binding of an MBP-specific antibody to MBP and the aptamer was found more sensitive than a commercial antibody. In addition, we showed the ability of the aptamer to detect myelin-rich regions in paraffin-embedded mouse brain tissue. Therefore, the MBP-binding activity of the selected oligonucleotide may prove useful as a tool for life science and medical research for myelin detection and might be a good lead for testing it in autoimmune diseases such as multiple sclerosis.

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“…In one study, in vivo knockdown of 80% was achieved in CD4 T cells [7], while in another vaccine-activated CD8+ T cells were knocked down by 50%. Moreover, aptamers, which usually have nanomolar affinity, can be selected for agonistic or antagonistic activity against their target [11,12] and can be covalently linked or conjugated to other aptamers, peptides, small molecules including toxins, and RNAs, providing a flexible platform for targeted manipulation of cells recognized by the aptamer. Here we describe the use of aptamers and aptamer conjugates for immune modulation.…”

Section: Introductionmentioning

confidence: 99%

Manipulating the in vivo immune response by targeted gene knockdown

Lieberman

2015

Current Opinion in Immunology

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Aptamers, nucleic acids selected for high affinity binding to proteins, can be used to activate or antagonize immune mediators or receptors in a location and cell-type specific manner and to enhance antigen presentation. They can also be linked to other molecules (other aptamers, siRNAs or miRNAs, proteins, toxins) to produce multifunctional compounds for targeted immune modulation in vivo. Aptamer-siRNA chimeras (AsiCs) that induce efficient cell-specific knockdown in immune cells in vitro and in vivo can be used as an immunological research tool or potentially as an immunomodulating therapeutic.

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Antagonistic RNA aptamer specific to a heterodimeric form of human interleukin-17A/F

Cited by 19 publications

References 40 publications

Selection and Application of ssDNA Aptamers to Detect Active TB from Sputum Samples

Selection and Application of ssDNA Aptamers to Detect Active TB from Sputum Samples

Myelin Basic Protein and a Multiple Sclerosis-related MBP-peptide Bind to Oligonucleotides

Manipulating the in vivo immune response by targeted gene knockdown

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