@article{ETD,
      school = {Ph.D.},
      author = {Vonada, Anne},
      url = {http://digitalcollections.ohsu.edu/record/42385},
      title = {A novel method of drug-mediated in vivo selective  hepatocyte expansion for liver-directed gene and cell  therapy},
      publisher = {Oregon Health and Science University},
      abstract = {Liver-directed gene and cell therapies represent a  promising therapeutic strategy for many genetic disorders.  However, they are hampered by inefficiency. The problem of  inefficiency could be overcome by providing a selective  growth advantage to corrected cells to allow them to  repopulate the liver. This work aimed to characterize a  novel method for in vivo selective expansion of hepatocytes  using the common medication acetaminophen (APAP). In the  liver, APAP is metabolized by cytochrome P450 enzymes to  form a hepatotoxic intermediate. Cytochrome P450 enzymes  require a cofactor, cytochrome P450 reductase (Cypor), for  activity. Therefore, knockout of Cypor prevents APAP  toxicity. A rare population of Cypor-deficient cells can  thus be selectively expanded in vivo by APAP treatment.  This work describes the application of this strategy to  both liver-directed viral gene therapy and hepatocyte  transplantation. },
      number = {ETD},
      doi = {https://doi.org/10.6083/bpxhc42385},
      recid = {42385},
      address = {2023-12-15},
}