000000747 001__ 747
000000747 005__ 20260120144838.0
000000747 0247_ $$2DOI$$a10.6083/M4348HC9
000000747 037__ $$aETD
000000747 245__ $$aA newly designed AAV-rDNA vector for persistent therapy in genetic liver diseases
000000747 260__ $$bOregon Health and Science University
000000747 269__ $$a2012
000000747 336__ $$aDissertation
000000747 502__ $$bPh.D.
000000747 520__ $$aAdeno-associated virus (AAV) is widely used in gene therapy but has limited integration, reducing long-term transgene expression. We engineered an AAV-rDNA vector to enhance integration and tested it in HT1 and hemophilia B mouse models. AAV-rDNA achieved 10–30 times higher integration and functional expression than control vectors, rescuing disease at much lower doses and restoring normal liver function. Integration was site-specific within rDNA repeats, confirmed by sequencing. These findings demonstrate that AAV-rDNA vectors enable efficient, stable gene expression and represent a promising approach for treating genetic disorders requiring persistent correction.
000000747 540__ $$fCC BY
000000747 542__ $$fIn copyright - single owner
000000747 650__ $$aAcetoacetates$$013687
000000747 650__ $$aVirus Integration$$029300
000000747 650__ $$aLiver$$021580
000000747 650__ $$aTyrosinemias$$032196
000000747 650__ $$aDependovirus$$014224
000000747 650__ $$aGenetics$$019472
000000747 650__ $$aFactor IX$$018851
000000747 650__ $$aLiver Diseases$$021588
000000747 650__ $$aHemophilia B$$016644
000000747 650__ $$aDNA, Ribosomal$$018005
000000747 6531_ $$aadenoviruses
000000747 6531_ $$arecombinant dna
000000747 6531_ $$ablood coagulation factor ix
000000747 691__ $$aSchool of Medicine$$041369
000000747 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000000747 7001_ $$aWang, Zhongya$$uOregon Health and Science University$$041354
000000747 8564_ $$97738be76-1e11-4b5f-b46d-6836282d8859$$s2343622$$uhttps://digitalcollections.ohsu.edu/record/747/files/750_etd.pdf$$ePublic$$2b358c073ad43472a156bc7ac61fe66e5$$31
000000747 905__ $$a/rest/prod/70/79/57/70/707957706
000000747 909CO $$ooai:digitalcollections.ohsu.edu:747$$pstudent-work
000000747 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000747 980__ $$aTheses and Dissertations