METHOD FOR CONTINUOUS-INFUSION INTO THE PORTAL-VEIN OF MICE

Recombinant retroviral vectors are attractive for in vivo gene transfe r into the liver because they integrate into the host-cell genome, res ulting in permanent gene expression. Gene-transfer efficiency can be i mproved by increasing the number of retroviral particles delivered to hepatocytes, For this purpose, we report a mouse model for continuous infusion into the portal circulation permitting large-volume vector ad ministration, which will allow marked increase in gene-transfer effici ency. Continuous saline infusion was evaluated, using various paramete rs, and an infusion rate of 6 ml/24 h was found safe and well tolerate d for at least 2 weeks. No significant changes in liver and kidney fun ction and electrolyte balance were observed during the infusion. In ad dition to providing a valuable method for in vivo hepatic gene therapy , this model has a number of other potential applications, including m ouse studies of hepatic tumor therapy, pharmacology, toxicology, and l iver biology.