A protein therapeutic modality founded on molecular regulation.

dc.contributor.authorWright, Chapman M.en
dc.contributor.authorWright, R. Clayen
dc.contributor.authorEshleman, James R.en
dc.contributor.authorOstermeier, Marcen
dc.contributor.departmentBiological Systems Engineeringen
dc.date.accessioned2019-01-21T17:35:29Zen
dc.date.available2019-01-21T17:35:29Zen
dc.date.issued2011-09-19en
dc.date.updated2019-01-21T17:35:27Zen
dc.description.abstractThe exquisite specificity of proteins is a key feature driving their application to anticancer therapies. The therapeutic potential of another fundamental property of proteins, their ability to be regulated by molecular cues in their environment, is unknown. Here, we describe a synthetic biology strategy for designing protein therapeutics that autonomously activate a therapeutic function in response to a specific cancer marker of choice. We demonstrate this approach by creating a prodrug-activating enzyme that selectively kills human cancer cells that accumulate the marker hypoxia-inducible factor 1α. This property arises primarily through increased cellular accumulation of the enzyme in the presence of the marker. Our strategy offers a platform for the development of inherently selective protein therapeutics for cancer and other diseases.en
dc.description.versionPublished versionen
dc.format.extentPages 16206-16211en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1073/pnas.1102803108en
dc.identifier.eissn1091-6490en
dc.identifier.issn0027-8424en
dc.identifier.issue39en
dc.identifier.orcidWright, Robert [0000-0001-7125-3943]en
dc.identifier.otherPMC3182702en
dc.identifier.other1102803108 (PII)en
dc.identifier.pmid21930952en
dc.identifier.urihttp://hdl.handle.net/10919/86813en
dc.identifier.volume108en
dc.language.isoenen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/21930952en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectMD Multidisciplinaryen
dc.subject.meshCell Line, Tumoren
dc.subject.meshHumansen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshColonic Neoplasmsen
dc.subject.meshRecombinant Proteinsen
dc.subject.meshFemaleen
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subuniten
dc.titleA protein therapeutic modality founded on molecular regulation.en
dc.title.serialProceedings of the National Academy of Sciences of the United States of Americaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherResearch Support, N.I.H., Extramuralen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biological Systems Engineeringen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
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