The generation and biological activity of a long-lasting recombinant human interferon-1

The previously generated recombinant human (rh) interferon (IFN)-1 protein has a short half-life, and this feature makes it challenging to conduct studies on potential clinical applications for rhIFN-1. In an attempt to overcome this difficulty, we constructed a long-life' version of rhIFN-1. This modified rhIFN-1, named rhIFN-1-CTPON, has a human chorionic gonadotropin subunit carboxyl-terminal peptide (CTP) and an N-glycosylation sequence linked to its C-terminus. We confirmed the sequence of rhIFN-1-CTPON by mass spectrometry and then measured its biological activities. The results show that rhIFN-1-CTPON had antiviral activity and anti-proliferation activity in vitro that were similar to those of rhIFN-1 and that it similarly promoted natural killer cell cytotoxicity. Notably, the in vivo half-life of rhIFN-1-CTPON was determined to be 3-fold higher than that of rhIFN-1. We also assessed the anti-hepatitis B virus activity of rhIFN-1-CTPON; it was able to inhibit the production of the antigens HBs-Ag and HBe-Ag and induce antiviral gene expression. In conclusion, rhIFN-1-CTPON has a longer half-life than rhIFN-1 and has similar biological activities, so rhIFN-1-CTPON is an appropriate substitute for rhIFN-1 in the further study of potential clinical applications for rhIFN- 1.