000000840 001__ 840
000000840 005__ 20260410124452.0
000000840 0247_ $$2DOI$$a10.6083/M42N508G
000000840 037__ $$aETD
000000840 245__ $$aAAV based site-specific integration in vivo
000000840 260__ $$bOregon Health and Science University
000000840 269__ $$a2007
000000840 336__ $$aThesis
000000840 502__ $$bM.S.
000000840 502__ $$gCell & Developmental Biology (sunsetting)
000000840 520__ $$aRecombinant adeno-associated virus (AAV) vectors predominantly remain episomal and integrate randomly at low frequency, raising safety concerns for gene therapy. We developed an rDNA-targeted AAV vector designed for site-specific integration via homologous recombination. An hFah expression cassette flanked by rDNA homology rescued Fah⁻/⁻ mice at significantly lower doses than conventional AAV, with stable phenotypic correction confirmed by serial transplantation and site-specific junction PCR. Targeted vectors showed enhanced persistence after partial hepatectomy and enabled systemic site-specific integration in multiple tissues. This strategy provides a highly efficient, low-dose platform for durable gene therapy.
000000840 540__ $$fCC BY
000000840 542__ $$fIn copyright - single owner
000000840 650__ $$aDNA, Ribosomal$$018005
000000840 650__ $$aMice$$036842
000000840 650__ $$aDependovirus$$014224
000000840 650__ $$aAdenoviruses, Human$$014253
000000840 650__ $$aGenetic Therapy$$028314
000000840 650__ $$aMutagenesis, Site-Directed$$029043
000000840 691__ $$aSchool of Medicine$$041369
000000840 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000000840 7001_ $$aWang, Zhongya$$uOregon Health and Science University$$041354
000000840 8564_ $$9bc259ab0-5f17-446d-ba8f-ead6f7388600$$s1107097$$uhttps://digitalcollections.ohsu.edu/record/840/files/843_etd.pdf$$ePublic$$2bed3e70db546ba670cc931ed9e918669$$31
000000840 901__ $$a<p>These documents are archival records. They are retained for historical reference only. </p><p><b>Need an accessible version? Use the ‘Get Accessible Copy’ link above.</b></p>
000000840 905__ $$a/rest/prod/qb/98/mf/50/qb98mf50f
000000840 909CO $$ooai:digitalcollections.ohsu.edu:840$$pstudent-work
000000840 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000840 980__ $$aTheses and Dissertations