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dc.contributor.authorKeittisak Suwanen_US
dc.contributor.authorTeerapong Yataen_US
dc.contributor.authorSajee Waramiten_US
dc.contributor.authorJustyna M. Przystalen_US
dc.contributor.authorCharlotte A. Stonehamen_US
dc.contributor.authorKaoutar Bentayebien_US
dc.contributor.authorPaladd Asavaruten_US
dc.contributor.authorAitthiphon Chongchaien_US
dc.contributor.authorPeraphan Pothachareonen_US
dc.contributor.authorKoon Yang Leeen_US
dc.contributor.authorSupachai Topanuraken_US
dc.contributor.authorTracey L. Smithen_US
dc.contributor.authorJuri G. Gelovanien_US
dc.contributor.authorRichard L. Sidmanen_US
dc.contributor.authorRenata Pasqualinien_US
dc.contributor.authorWadih Arapen_US
dc.contributor.authorAmin Hajitouen_US
dc.description.abstractCopyright © 2019 the Author(s). Published by PNAS. Bacteriophage (phage) have attractive advantages as delivery systems compared with mammalian viruses, but have been considered poor vectors because they lack evolved strategies to confront and overcome mammalian cell barriers to infective agents. We reasoned that improved efficacy of delivery might be achieved through structural modification of the viral capsid to avoid pre- and postinternalization barriers to mammalian cell transduction. We generated multifunctional hybrid adeno-associated virus/phage (AAVP) particles to enable simultaneous display of targeting ligands on the phage's minor pIII proteins and also degradation-resistance motifs on the very numerous pVIII coat proteins. This genetic strategy of directed evolution bestows a next-generation of AAVP particles that feature resistance to fibrinogen adsorption or neutralizing antibodies and ability to escape endolysosomal degradation. This results in superior gene transfer efficacy in vitro and also in preclinical mouse models of rodent and human solid tumors. Thus, the unique functions of our next-generation AAVP particles enable improved targeted gene delivery to tumor cells.en_US
dc.titleNext-generation of targeted AAVP vectors for systemic transgene delivery against canceren_US
article.title.sourcetitleProceedings of the National Academy of Sciences of the United States of Americaen_US
article.volume116en_US College Londonen_US Universityen_US Cancer Institute of New Jerseyen_US State Universityen_US Medical Schoolen_US Mai Universityen_US Cancer Institute of New Jerseyen_US New Jersey Medical Schoolen_US
Appears in Collections:CMUL: Journal Articles

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