ヒトで使用する遺伝子組み換えタンパク質の適切な糖鎖化：発現系の選択の影響

遺伝子組み換えでタンパク質を産生する際の糖鎖化の問題について、発現システムの選択の重要性を２００４年に訴えている論文です

２００４年、子宮頸がんワクチンの治験はすでに始まっていましたので、子宮頸がんワクチンの開発にこの問題についてどれだけ考察されているかは甚だ疑問です。

 

 

Mol Biotechnol. 2004 Nov;28(3):241-55.

Appropriate glycosylation of recombinant proteins for human use: implications of choice of expression system.

Brooks SA¹.

Author information

Abstract

One of the commonest and least well understood posttranslational modifications of proteins is their glycosylation. Human glycoproteins are glycosylated with a bewilderingly heterogeneous array of complex N- and O-linked glycans, which are the product of the coordinated activity of enzymes resident in the endoplasmic reticulum and Golgi apparatus of the cell. Glycosylation of proteins is highly regulated and changes during differentiation, development, under different physiological--and cell culture--conditions and in disease. The glycosylation of recombinant proteins, especially those destined for potential administration to human subjects, is of critical importance. Glycosylation profoundly affects biological activity, function, clearance from circulation, and crucially, antigenicity. The cells of nonhuman species do not glycosylate their proteins in the same way as human cells do. In many cases, the differences are profound. Overall, the species most distant to humans in evolutionary terms, such as bacteria, yeasts, fungi, insects and plants--the species used most commonly in expression systems--have glycosylation repertoires least like our own. This review gives a brief overview of human N- and O-linked protein glycosylation, summarizes what is known of the glycosylation potential of the cells of nonhuman species, and presents the implications for the biotechnology industry.