烟草细胞中高效表达的药用蛋白可以提高血清的半衰期

High-yield Expression of Therapeutic Proteins with Extended Serum Half-life in Tobacco Cells

摘要:

本研究发现了一种生产具有生物功效的药用蛋白的方法。在培养的烟草细胞中表达如干扰素a2b (IFNa2)和人类生长激素(hGH)等阿拉伯半乳糖聚糖糖蛋白嵌合体, 不仅可以提高药用蛋白的产量, 还可以延长血清的半衰期。这种嵌合糖蛋白的分泌量是没有糖基化时蛋白产量的500~1800倍。更重要的是, 这种嵌合糖蛋白不仅可以使体内血清的半衰期延长13倍, 同时它们的生物活性与天然的干扰素和人类生长激素很相近。

关键词:植物细胞培养, 重组蛋白, 糖基化羟脯胺酸, 半衰期

Abstract:

We developed a new method that yields biologically potent therapeutic proteins such as interferon a2b (IFNa2) and human growth hormone (hGH) in high yields and with increased serum half-lives when expressed as arabinogalactan-protein (AGP) chimeras in cultured tobacco cells. The chimeric glycoproteins typically gave 500–1800 fold greater secreted yields than their non-glycosylated controls. Importantly, the chimeric glycoproteins showed an increased in vivo serum half-life of up to 13 fold while their biological activities remain similar to native IFNα2 and hGH.

Key words:plant cell culture, recombinant protein, hydroxyproline-O-glycosylation, half-life