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Evaluation of RNA-knockdown strategies for modulation of cytochrome P450 reductase activity in mouse hepatocytes

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)416-421
JournalJournal of RNAi and Gene Silencing.
Volume6
Issue number2
StatePublished - 2010

Abstract

Transgenic technologies can provide important animal models for studying drug-metabolizing enzymes. Our overall aim was to generate versatile cell and animal systems that exhibited varying levels of cytochrome P450 oxidoreductase (POR) activity, more accurately modelling the human population for pharmacological and toxicology studies. Towards this goal we evaluated RNA-interference constructs designed for use in vitro and in vivo for reducing POR activity in hepatocytes. This study clearly demonstrates that both POR protein level and reductase activity can be significantly knocked down in Hepa-1 cells in vitro, while highlighting the difficulty in predicting knockdown efficiency in transgenic animals. The high levels of embryonic lethality observed, and inability to produce multi-copy transgenic animals indicates that high levels of shRNA expression may be detrimental to embryonic development.

    Research areas

  • RNA-interference, drug metabolism, lentivirus vectors, liver metabolism, transgenic mice

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