[Correction of bilirubin glucuronyl transferase in Gunn rats by gene transfer in the liver using retroviral vectors]

Abstract

The in vivo procedure for retrovirus-mediated gene transfer into rat liver allows genetic modification of 1 to 5% hepatocytes and the expression of a foreign gene for more than one year. We have used the Gunn rat as a model of the human Crigler-Najjar type I syndrome to assess the pertinence of this approach for the treatment of severe liver genetic diseases. After transfer of the rat bilirubin uridin diphosphate-glucuronosyl transferase cDNA into hepatocytes, 15 Gunn rats were examined during several months and sacrificed. Bilirubin glucuronides were excreted in the bile of all recipients, and serum bilirubin levels were significantly reduced in the treated population. The decrease was more than 40% in 5 of the 15 rats. These date showed that long term expression of a therapeutic protein can be obtain after in vivo retrovirus-mediated gene transfer into the liver.