TY  - GEN
N2  - 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. 
DO  - 10.6083/bpxhc42385
DO  - doi
AB  - 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. 
AD  - Oregon Health and Science University
T1  - A novel method of drug-mediated in vivo selective hepatocyte expansion for liver-directed gene and cell therapy
DA  - 2023-12-15
AU  - Vonada, Anne
L1  - https://digitalcollections.ohsu.edu/record/42385/files/Vonada.Anne.2023.pdf
PB  - Oregon Health and Science University
LA  - eng
PY  - 2023-12-15
ID  - 42385
L4  - https://digitalcollections.ohsu.edu/record/42385/files/Vonada.Anne.2023.pdf
KW  - Genetic Therapy
KW  - Phenylketonurias
KW  - Acetaminophen
KW  - Genetic Therapy
KW  - cell therapy
KW  - hepatocyte transplantation
TI  - A novel method of drug-mediated in vivo selective hepatocyte expansion for liver-directed gene and cell therapy
Y1  - 2023-12-15
L2  - https://digitalcollections.ohsu.edu/record/42385/files/Vonada.Anne.2023.pdf
LK  - https://digitalcollections.ohsu.edu/record/42385/files/Vonada.Anne.2023.pdf
UR  - https://digitalcollections.ohsu.edu/record/42385/files/Vonada.Anne.2023.pdf
ER  -