Tamarin alpha-interferon is active in mouse liver upon intramuscular gene delivery

Background The hepatitis C virus (HCV) is responsible for a severe and widespread form of hepatitis for which a durable and effective therapy has not yet been established. The only approved therapy against hepatitis C, alpha‐interferon protein intramuscular administration, presents numerous drawbacks that might be overcome by adopting a gene therapy approach. HCV exclusively infects humans and chimpanzees, hence an acceptable animal model for hepatitis C pharmacological studies is not available. Recently, tamarins infected by GB virus B (GBV‐B) have been proposed as a surrogate animal model for HCV infection. The aim of the present study was the production of tamarin interferon (tIFN) through delivery of tIFN‐coding DNA to evaluate the feasibility of a gene therapy approach based on IFN electro‐gene transfer (EGT) in future studies with primates. Methods Production and biological activity of cloned tamarin interferon was monitored in cultured cells upon transfection and in mice upon muscle EGT of the corresponding plasmid DNA, respectively. Results A tamarin gene encoding a protein homologous to human interferon‐alpha2 (hIFN‐α2) has been cloned. The tamarin IFN‐α (tIFN‐α) protein shows antiviral activity in a cell‐based assay. Upon EGT of the corresponding gene in mouse muscles, tIFN‐α is detectable at high levels in serum for at least 4 months. Most important, activity of tIFN, measured as enhancement of mRNA levels of genes induced by type I IFNs, is also detectable in the liver of EGT‐treated mice. Conclusion The present study demonstrates that the delivery of tIFN‐α DNA via intramuscular injection yields a functional protein able to produce biological effects inside a remote target organ, the liver. This finding, besides the specific purpose of the present study, is of general relevance with a view to establishing therapeutic protocols based on EGT. Copyright © 2001 John Wiley & Sons, Ltd.