GENE TRANSFER INTO PRIMARY HEPATOCYTES FOR SOMATIC GENE THERAPY

Gene transfer into human epidermis as an experimental model for somatic gene therapy.

A novel mechanism for achieving transgene persistence in vivo after somatic gene transfer into hepatocytes.

Infusion of hepatocyte-specific DNA-protein complexes into rats leads to transient recombinant gene expression in liver. The eventual deterioration of gene expression is due in part to instability of the targeted DNA. In a previous report, we noted retention of transgene sequences in liver and persistent recombinant gene expression when the animals were subjected to partial hepatectomy followin...

Hepatic gene therapy: efficient retroviral-mediated gene transfer into rat hepatocytes in vivo.

The rat is an excellent model for gene therapy because there are many rat models for human diseases. We have developed a simple and efficient method to deliver genes to the rat liver using recombinant retroviral vectors. A 70% partial hepatectomy followed by retroviral infusion into the portal vein results in 10-15% hepatocyte transduction in vivo. This is 10 times more efficient than in the mo...

"Hepatic Gene Therapy: Efficient Retroviral Mediated Gene Transfer into Rat Hepatocytes

Towards liver-directed gene therapy: retrovirus-mediated gene transfer into human hepatocytes.

Liver-directed gene therapy is being considered in the treatment of inherited metabolic diseases. One approach we are considering is the transplantation of autologous hepatocytes that have been genetically modified with recombinant retroviruses ex vivo. We describe, in this report, techniques for isolating human hepatocytes and efficiently transducing recombinant genes into primary cultures. He...