Mx1 and IP-10: Biomarkers to Measure IFN-β Activity in Mice Following Gene-Based Delivery

Recombinant interferon-β (IFN-β) protein is used successfully for the treatment of multiple sclerosis (MS). Gene therapy might be an alternative approach to overcome drawbacks occurring with IFN-β protein therapy. A critical issue in developing a new approach is detection of biologically active IFN-β in preclinical models. The goal of the present study was to determine if Mx1 and IP-10, which are known to be activated after IFN-β treatment in humans, can be used as biomarkers in mice. In three in vivo experiments, the correlation between different methods of murine IFN-β (MuIFN-β) delivery and biomarker induction was studied: (1) bolus protein delivery by intravenous (i.v.) or intramuscular (i.m.) injection, (2) gene-based delivery of IFN- β by i.m. injection of plasmid DNA, followed by electroporation, and (3) gene-based delivery of IFN-β by i.m. injection of adenovirus-associated type 1 (AAV1). Short-term induction of Mx1 mRNA and IP-10 was observed after treatment with bolus MuIFN-β protein. Long-term ...