Tunable Protease-Activatable Virus Nanonodes

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dc.citation.firstpage4740en_US
dc.citation.issueNumber5en_US
dc.citation.journalTitleACS Nanoen_US
dc.citation.lastpage4746en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorJudd, Justinen_US
dc.contributor.authorHo, Michelle L.en_US
dc.contributor.authorTiwari, Abhinaven_US
dc.contributor.authorGomez, Eric J.en_US
dc.contributor.authorDempsey, Christopheren_US
dc.contributor.authorVliet, Kim Vanen_US
dc.contributor.authorIgoshin, Oleg A.en_US
dc.contributor.authorSilberg, Jonathan J.en_US
dc.contributor.authorAgbandje-McKenna, Mavisen_US
dc.contributor.authorSuh, Junghaeen_US
dc.date.accessioned2015-07-09T20:14:50Zen_US
dc.date.available2015-07-09T20:14:50Zen_US
dc.date.issued2014en_US
dc.description.abstractWe explored the unique signal integration properties of the self-assembling 60-mer protein capsid of adeno-associated virus (AAV), a clinically proven human gene therapy vector, by engineering proteolytic regulation of virusﾖreceptor interactions such that processing of the capsid by proteases is required for infection. We find the transfer function of our engineered protease-activatable viruses (PAVs), relating the degree of proteolysis (input) to PAV activity (output), is highly nonlinear, likely due to increased polyvalency. By exploiting this dynamic polyvalency, in combination with the self-assembly properties of the virus capsid, we show that mosaic PAVs can be constructed that operate under a digital AND gate regime, where two different protease inputs are required for virus activation. These results show viruses can be engineered as signal-integrating nanoscale nodes whose functional properties are regulated by multiple proteolytic signals with easily tunable and predictable response surfaces, a promising development toward advanced control of gene delivery.en_US
dc.identifier.citationJudd, Justin, Ho, Michelle L., Tiwari, Abhinav, et al.. "Tunable Protease-Activatable Virus Nanonodes." <i>ACS Nano,</i> 8, no. 5 (2014) American Chemical Society: 4740-4746. http://dx.doi.org/10.1021/nn500550q.en_US
dc.identifier.doihttp://dx.doi.org/10.1021/nn500550qen_US
dc.identifier.urihttps://hdl.handle.net/1911/80871en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.subject.keywordgene deliveryen_US
dc.subject.keywordmatrix metalloproteinaseen_US
dc.subject.keywordlogic gateen_US
dc.subject.keywordadeno-associated virusen_US
dc.subject.keywordmosaic capsiden_US
dc.titleTunable Protease-Activatable Virus Nanonodesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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