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dc.contributor.advisorDuan, Dongshengeng
dc.contributor.authorGhosh, Arkasubhra, 1977-eng
dc.date.issued2007eng
dc.date.submitted2007 Falleng
dc.description"December 2007"eng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionVita.eng
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2007.eng
dc.description.abstractAdeno associated viruses (AAV) have recently been demonstrated as a very promising gene delivery vehicle. But the limited packaging capacity of AAV vectors (4̃.7kb) hinders their application for diseases involving large genes such as those responsible for Duchenne muscular dystrophy and cystic fibrosis. To overcome this hurdle, the trans-splicing and overlapping dual vector methods were developed to expand the packaging capacity of AAV. It has been demonstrated that certain expression limiting barriers affect transduction from these dual vectors. The trans-splicing method requires an optimal gene splitting site and the overlapping method requires a highly recombinogenic domain in the middle of the gene for high levels of transduction. To overcome these limitations of dual vectors, we developed a novel transsplicing/ overlapping hybrid vector system that can efficiently reconstitute any large gene. The experimental data demonstrate that the hybrid vector system improves gene expression compared to the traditional dual vectors. The study also demonstrates that the rationally designed transsplicing AAV vectors can be successfully used for body-wide gene delivery. Taken together, this study outlines the considerations to be taken into account for rational design of split gene vectors that would be capable of efficient transgene expression.eng
dc.description.bibrefIncludes bibliographical referenceseng
dc.identifier.merlinb66635548eng
dc.identifier.oclc314387342eng
dc.identifier.urihttps://doi.org/10.32469/10355/4712eng
dc.identifier.urihttps://hdl.handle.net/10355/4712
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
dc.subject.meshMuscular Dystrophy, Duchenne -- therapyeng
dc.subject.meshMuscular Dystrophy, Duchenne -- geneticseng
dc.subject.meshTransduction, Geneticeng
dc.subject.meshCystic Fibrosis -- therapyeng
dc.subject.meshGene Therapy -- methodseng
dc.subject.meshCystic Fibrosis -- geneticseng
dc.subject.meshGenetic Vectorseng
dc.titleRational design of split gene vectors to expand the packaging capacity of adeno-associated viral vectorseng
dc.typeThesiseng
thesis.degree.disciplineMicrobiology (Medicine) (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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