Lethal saturation

• • Liver directed
  • • Luc-shRNA + AAV8-Luc or hAAT+shRNA-hAAT
    • • Low dose (2x1011) : OK
      • High dose (1012): Toxicity
  • Toxicity ~ levels of miR-122 or let7a
  • ~ independent of liver injury
  • Exportin5 overexpression increased silencing again