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dc.contributor.authorYang, Nicole Jie Yeon
dc.contributor.authorSklaviadis, Demetra
dc.contributor.authorWittrup, Karl Dane
dc.contributor.authorGui, Dan Yi
dc.contributor.authorVander Heiden, Matthew G.
dc.contributor.authorLiu, David V.
dc.date.accessioned2016-12-15T15:27:23Z
dc.date.available2016-12-15T15:27:23Z
dc.date.issued2015-04
dc.date.submitted2014-12
dc.identifier.issn1543-8384
dc.identifier.issn1543-8392
dc.identifier.urihttp://hdl.handle.net/1721.1/105826
dc.description.abstractPerfringolysin O (PFO) is a member of the cholesterol-dependent cytolysin (CDC) family of bacterial pore-forming proteins, which are highly efficient in delivering exogenous proteins to the cytoplasm. However, the indiscriminate and potent cytotoxicity of PFO limits its practical use as an intracellular delivery system. In this study, we describe the design and engineering of a bispecific, neutralizing antibody against PFO, which targets reversibly attenuated PFO to endocytic compartments via receptor-mediated internalization. This PFO-based system efficiently mediated the endosomal release of a co-targeted gelonin construct with high specificity and minimal toxicity in vitro. Consequently, the therapeutic window of PFO was improved by more than 5 orders of magnitude. Our results demonstrating that the activity of pore-forming proteins can be controlled by antibody-mediated neutralization present a novel strategy for utilizing these potent membrane-lytic agents as a safe and effective intracellular delivery vehicle.en_US
dc.description.sponsorshipMassachusetts Institute of Technology/National Institute of General Medical Sciences Biotechnology Training Programen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant CA101830)en_US
dc.language.isoen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/mp500797nen_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.sourcePMCen_US
dc.titleAntibody-Mediated Neutralization of Perfringolysin O for Intracellular Protein Deliveryen_US
dc.typeArticleen_US
dc.identifier.citationYang, Nicole J. et al. “Antibody-Mediated Neutralization of Perfringolysin O for Intracellular Protein Delivery.” Molecular Pharmaceutics 12.6 (2015): 1992–2000.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorYang, Nicole Jie Yeon
dc.contributor.mitauthorLiu, David V
dc.contributor.mitauthorSklaviadis, Demetra
dc.contributor.mitauthorWittrup, Karl Dane
dc.contributor.mitauthorGui, Dan Yi
dc.contributor.mitauthorVander Heiden, Matthew G.
dc.relation.journalMolecular Pharmaceuticsen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsYang, Nicole J.; Liu, David V.; Sklaviadis, Demetra; Gui, Dan Y.; Vander Heiden, Matthew G.; Wittrup, K. Daneen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-0882-7761
dc.identifier.orcidhttps://orcid.org/0000-0003-2398-5896
dc.identifier.orcidhttps://orcid.org/0000-0003-0130-3428
dc.identifier.orcidhttps://orcid.org/0000-0002-6702-4192
mit.licensePUBLISHER_POLICYen_US


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