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Development of an scAAVIGF-I gene therapeutic vector for the enhancement of cartilage repair

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dc.contributor.authorHemphill, Daniel, author
dc.contributor.authorGoodrich, Laurie, advisor
dc.contributor.authorMcIlwraith, C. Wayne, advisor
dc.contributor.authorSamulski, R. Jude, committee member
dc.contributor.authorSlayden, Ric, committee member
dc.contributor.authorJames, Sue, committee member
dc.date.accessioned2007-01-03T06:31:18Z
dc.date.available2015-09-30T06:30:24Z
dc.date.issued2014
dc.description.abstractIn this work, we hypothesize scAAVIGF-I can be efficiently engineered and used as a gene therapeutic vector to transduce cartilage and synovium and elicit biochemical changes consistent with cartilage repair mechanisms. Here we show joint tissues are permissive to serotype specific, efficient AAV transduction. This is in agreement with previous in vitro and in vivo studies demonstrating AAV as an efficient vector for gene therapy. Interestingly, we show a clinically relevant occurrence of pre-existing, serotype specific AAV neutralization. After creation of an optimized scAAVIGF-I vector, we show transduction of chondrocytes results in significantly increased IGF-I levels that translate to biochemical changes in glycosaminoglycan and proteoglycan content. NextGen RNA transcriptome sequencing and PCR analysis revealed significant differential regulation of genes in pathways including cartilage biology and cell death, but not significant in other pathways associated with IGF-I treatment such as Wnt and Akt regulation. The problem addressed by this research is ultimately answered in that scAAVIGF-I can both efficiently transduce joint tissue and increase IGF-I concentrations sufficiently to cause biochemical changes indicative of healthy cartilage, and the pathways associated with upregulation of IGF-I gene therapy are revealed.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierHemphill_colostate_0053A_12622.pdf
dc.identifier.urihttp://hdl.handle.net/10217/83777
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectcartilage
dc.subjectAAV
dc.subjectgene therapy
dc.subjectIGF-I
dc.titleDevelopment of an scAAVIGF-I gene therapeutic vector for the enhancement of cartilage repair
dc.typeText
dcterms.embargo.expires2015-09-30
dcterms.embargo.terms2015-09-30
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBioengineering
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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