Expression in Pichia pastoris and properties of human serum albumin-interferon alpha2b chimera.
- Author:
Shao-Hong CHANG
1
;
Xin GONG
;
Zhi-Yu YANG
;
Tong-Ying WANG
;
Guo-Chang MA
;
Qing-Jun MA
;
Jun WU
Author Information
1. Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Bioreactors;
microbiology;
Fermentation;
Humans;
Interferon-alpha;
biosynthesis;
genetics;
Macaca fascicularis;
Pichia;
genetics;
metabolism;
Recombinant Fusion Proteins;
biosynthesis;
genetics;
pharmacokinetics;
Recombinant Proteins;
Serum Albumin;
biosynthesis;
genetics
- From:
Chinese Journal of Biotechnology
2006;22(2):173-179
- CountryChina
- Language:Chinese
-
Abstract:
To reduce the serum clearance of interferon alpha2b, a chimeric gene encoding an human serum albumin(HSA)--human interferon alpha2b(IFNalpha2b) fusion protein was overexpressed in Pichia pastoris. After fermentation in a 5L bioreactor, the fusion protein, capable of cross-reacting with anti-IFN alpha and anti-HSA antibody, was purified from the culture of the recombinant yeast by ultrafiltration, blue Sepharose affinity, phenyl hydrophobic interaction and Q ion exchange chromatography. Its IFNa2b moiety exhibits antiviral activity similar to that of recombinant human IFNa2b. In Cynomolgus monkeys model, The fusion protein was detectable in plasma, even 336h after a single does of 90 microg/kg injection intravenously or subcutaneously. The elimination phase half-life of the fusion protein was 101h after intravenous injection and 68.2h after subcutaneous injection. Its Subcutaneous bioavailability was 67.9%. The enhanced pharmacokinetics of interferon a2b fused to human serum albumin suggest its promissing application in clinic medicine.
