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Article: Identification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signalling

TitleIdentification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signalling
Authors
KeywordsG-quadruplex
Isothermal titration calorimetry (ITC)
Sclerosteosis
Sclerostin
Systematic evolution of ligands by exponential enrichment (SELEX)
Wnt signalling
Issue Date2011
PublisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.org
Citation
Biochemical Journal, 2011, v. 434 n. 3, p. 493-501 How to Cite?
AbstractSclerostin is an extracellular negative regulator of bone formation that is a recognized therapeutic target for osteoporosis therapy. In the present study, we performed DNA aptamer selection against sclerostin, then characterized aptamer-sclerostin binding and the ability to inhibit sclerostin function in cell culture. We show that a selected DNA aptamer was highly selective for binding to sclerostin with affinities in the nanomolar range as determined by solid-phase assays and by isothermal titration calorimetry. Binding between sclerostin and the aptamer was exothermic and enthalpically driven. CD confirmed that the aptamer had temperature-dependent parallel G-quadruplex characteristics. The aptamer was stabilized with 3′ inverted thymidine to investigate efficacy at inhibiting sclerostin function in cell culture. The stabilized DNA aptamer showed potent and specific dose-dependent inhibition of sclerostin's antagonistic effect on Wnt activity using a reporter assay. Taken together, the present findings suggest an alternative approach to inhibiting sclerostin function with therapeutic potential. © The Authors Journal compilation © 2011 Biochemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/133578
ISSN
2015 Impact Factor: 3.562
2015 SCImago Journal Rankings: 2.582
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 7488/06M
Area of Excellence GrantAoE/M-04/04
Funding Information:

This work was supported by the Hong Kong Research Grants Council under the General Research Fund scheme [grant number HKU 7488/06M] and an Area of Excellence Grant [grant number AoE/M-04/04].

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorShum, KTen_HK
dc.contributor.authorChan, Cen_HK
dc.contributor.authorLeung, CMen_HK
dc.contributor.authorTanner, JAen_HK
dc.date.accessioned2011-05-24T02:11:12Z-
dc.date.available2011-05-24T02:11:12Z-
dc.date.issued2011en_HK
dc.identifier.citationBiochemical Journal, 2011, v. 434 n. 3, p. 493-501en_HK
dc.identifier.issn0264-6021en_HK
dc.identifier.urihttp://hdl.handle.net/10722/133578-
dc.description.abstractSclerostin is an extracellular negative regulator of bone formation that is a recognized therapeutic target for osteoporosis therapy. In the present study, we performed DNA aptamer selection against sclerostin, then characterized aptamer-sclerostin binding and the ability to inhibit sclerostin function in cell culture. We show that a selected DNA aptamer was highly selective for binding to sclerostin with affinities in the nanomolar range as determined by solid-phase assays and by isothermal titration calorimetry. Binding between sclerostin and the aptamer was exothermic and enthalpically driven. CD confirmed that the aptamer had temperature-dependent parallel G-quadruplex characteristics. The aptamer was stabilized with 3′ inverted thymidine to investigate efficacy at inhibiting sclerostin function in cell culture. The stabilized DNA aptamer showed potent and specific dose-dependent inhibition of sclerostin's antagonistic effect on Wnt activity using a reporter assay. Taken together, the present findings suggest an alternative approach to inhibiting sclerostin function with therapeutic potential. © The Authors Journal compilation © 2011 Biochemical Society.en_HK
dc.languageengen_US
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.orgen_HK
dc.relation.ispartofBiochemical Journalen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe final version of record is available at http://www.biochemj.org/bj/434/0493/bj4340493.htm-
dc.subjectG-quadruplexen_HK
dc.subjectIsothermal titration calorimetry (ITC)en_HK
dc.subjectSclerosteosisen_HK
dc.subjectSclerostinen_HK
dc.subjectSystematic evolution of ligands by exponential enrichment (SELEX)en_HK
dc.subjectWnt signallingen_HK
dc.subject.meshAptamers, Nucleotide - chemistry - pharmacology-
dc.subject.meshBone Morphogenetic Proteins - antagonists and inhibitors - chemistry-
dc.subject.meshCalorimetry-
dc.subject.meshThermodynamics-
dc.subject.meshWnt Proteins - physiology-
dc.titleIdentification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signallingen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0264-6021&volume=434&issue=3&spage=493&epage=501&date=2011&atitle=Identification+of+a+DNA+aptamer+that+inhibits+sclerostin%27s+antagonistic+effect+on+Wnt+signaling-
dc.identifier.emailTanner, JA:jatanner@hku.hken_HK
dc.identifier.authorityTanner, JA=rp00495en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1042/BJ20101096en_HK
dc.identifier.pmid21204783-
dc.identifier.scopuseid_2-s2.0-79952159933en_HK
dc.identifier.hkuros185114en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952159933&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume434en_HK
dc.identifier.issue3en_HK
dc.identifier.spage493en_HK
dc.identifier.epage501en_HK
dc.identifier.eissn1470-8728-
dc.identifier.isiWOS:000288613900013-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectDevelopmental genomics and skeletal research-
dc.relation.projectTargeting sclerostin with aptamer-based inhibitors as an approach to osteoporosis therapy-
dc.identifier.scopusauthoridShum, KT=20436474600en_HK
dc.identifier.scopusauthoridChan, C=36984609500en_HK
dc.identifier.scopusauthoridLeung, CM=41361402800en_HK
dc.identifier.scopusauthoridTanner, JA=35513993000en_HK

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