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dc.contributor.authorGollakota, Akhila
dc.date.accessioned2016-04-05T20:01:03Z
dc.date.available2016-04-05T20:01:03Z
dc.date.issued2015
dc.identifier.isbn9781321921380
dc.identifier.other1716390081
dc.identifier.urihttp://hdl.handle.net/10477/51812
dc.description.abstractThe aim of gene delivery research is to develop clinically pertinent vectors that can be used to combat elusive diseases. Moreover, gene modulation efficacy of nonviral vectors have been hindered by numerous in vitro and in vivo barriers that have resulted in subviral performance. Specifically, delivery a vector must overcome barriers including the extracellular milieu, cellular uptake, escape from the endosomal compartments prior to trafficking to lysosomes, cytosolic transport and nuclear localization of the genetic cargo. This thesis describes the development of a second generation of bio-synthetic gene delivery vectors in the context of conducting a systematic structure-function assessment using a library of mannosylated poly(beta-amino esters). Through a top-down screening methodology, an optimized polymer was selected on the basis of gene delivery efficacy and was then selected as the compositional background for the synthesis of a stratified molecular weight polymer library. Moreover, by eliminating contributions of polymer compositional background, we were able to analyze gene delivery efficacy as a function of (1) polymer molecular weight, (2) relative mannose content, (3) polymer-membrane biophysical properties, (4) APC-uptake specificity, and (5) serum inhibition. In summary, the flexibility and potential of the hybrid design featured in this work highlights the ability to systematically probe vector-associated properties for the development of translational gene delivery candidates.
dc.languageEnglish
dc.sourceDissertations & Theses @ SUNY Buffalo,ProQuest Dissertations & Theses Global
dc.subjectPure sciences
dc.subjectBiological sciences
dc.subjectApplied sciences
dc.subjectGene delivery
dc.subjectBio-synthetic hybrid
dc.subjectPoly beta amino esters
dc.titleMannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery
dc.typeDissertation/Thesis


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