Construction of a Novel Liver-Targeting Fusion Interferon by Incorporation of a Plasmodium Region I-Plus Peptide

Abstract EN

Interferon alpha (IFN α) exerts a multiplicity of biological actions including antiviral, immunomodulatory, and antiproliferative effects.

Administration of IFN α is the current treatment for chronic hepatitis B; however, therapy outcome has not been completely satisfactory.

The systemic effects of IFN α may account for its low in vivo biological activity and multiple adverse events.

The purpose of this study was to design a novel liver-targeting fusion interferon (IFN-CSP) by fusing IFN α2b with a Plasmodium region I-plus peptide, thus targeting the drug specifically to the liver.

The DNA sequence encoding IFN-CSP was constructed using improved splicing by overlapping extension-PCR method, and then cloned into the pET-21b vector for protein expression in E.

coli BL21 (DE3).

The recombinant protein was expressed as a His-tagged protein and purified using a combination of Ni affinity and HiTrap affinity chromatography at a purity of over 95%.

The final yield of biologically active IFN-CSP was up to 270 mg/L culture.

The purified recombinant protein showed anti-HBV activity and liver-targeting potentiality in vitro.

These data suggests that the novel fusion interferon IFN-CSP may be an excellent candidate as a liver-targeting anti-HBV agent.