000000720 001__ 720
000000720 005__ 20251218125608.0
000000720 0247_ $$2DOI$$a10.6083/M4K935JK
000000720 037__ $$aETD
000000720 245__ $$aNovel strategies to improve viral gene targeting and therapeutic liver repopulation in vivo
000000720 260__ $$bOregon Health and Science University
000000720 269__ $$a2012
000000720 336__ $$aDissertation
000000720 502__ $$bPh.D.
000000720 520__ $$aOrthotopic liver transplantation effectively treats pediatric metabolic diseases caused by hepatocyte-specific enzyme deficiencies, but donor scarcity, high cost, and lifelong immunosuppression limit its use. This dissertation explores alternative strategies: gene therapy and hepatocyte transplantation. First, recombinant adeno-associated viral (rAAV) vectors achieved stable in vivo gene targeting in neonatal and adult mice, with enhanced efficiency via transient inhibition of non-homologous end joining using vanillin and proteasome inhibition with bortezomib. Second, selective hepatocyte repopulation was demonstrated using CEHPOBA, enabling transient positive selection in wild-type livers. These findings highlight promising approaches for correcting metabolic liver disorders without whole-organ transplantation.
000000720 540__ $$fCC BY
000000720 542__ $$fIn copyright - single owner
000000720 650__ $$aHepatocytes$$032992
000000720 650__ $$aDNA Repair$$017990
000000720 650__ $$aDependovirus$$014224
000000720 650__ $$aLiver$$021580
000000720 650__ $$aTyrosinemias$$032196
000000720 650__ $$aTransplantation$$027278
000000720 650__ $$aHepatocytes$$032992
000000720 650__ $$aImmunosuppression Therapy$$020722
000000720 650__ $$aMetabolic Diseases$$022100
000000720 650__ $$aLiver Transplantation$$028835
000000720 6531_ $$agene therapy
000000720 6531_ $$adiseases
000000720 6531_ $$aliver cell
000000720 691__ $$aSchool of Medicine$$041369
000000720 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000000720 7001_ $$aPaulk, Nicole$$uOregon Health and Science University$$041354
000000720 8564_ $$9eed65512-aec9-4706-8134-9b5724d5f73a$$s2936534$$uhttps://digitalcollections.ohsu.edu/record/720/files/723_etd.pdf$$ePublic$$2c5697e7bd6ea0a23c620099decb3be0d$$31
000000720 905__ $$a/rest/prod/0r/96/73/77/0r967377q
000000720 909CO $$ooai:digitalcollections.ohsu.edu:720$$pstudent-work
000000720 980__ $$aTheses and Dissertations