Chiba Yasunori, Jigami Yoshifumi
Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 6, Tsukuba, Japan.
Curr Opin Chem Biol. 2007 Dec;11(6):670-6. doi: 10.1016/j.cbpa.2007.08.037. Epub 2007 Oct 23.
A suitable glycan structure is required for optimal protein-based therapeutics, such as antibody-dependent cell cytotoxicity in therapeutic antibodies, enzyme replacement therapy for lysosomal diseases, and controlled clearance of cytokines from the blood. Expressing proteins in unicellular organisms such as bacteria and yeast would be commercially advantageous compared with mammalian cells if these organisms could be engineered to produce human-type glycans. Although using bacteria and yeast to produce humanized glycoproteins and to conduct glycan remodeling of proteins remain a long-term goal for microbiologists and biochemists, recent studies in the field of microbial glycobiology in combination with synthetic chemical techniques suggest that this dream is close to being realized.
对于基于蛋白质的最佳治疗方法而言,需要合适的聚糖结构,例如治疗性抗体中的抗体依赖性细胞毒性、溶酶体疾病的酶替代疗法以及从血液中控制细胞因子的清除。如果能够对细菌和酵母等单细胞生物进行工程改造以产生人源型聚糖,那么与哺乳动物细胞相比,在这些生物中表达蛋白质将具有商业优势。尽管利用细菌和酵母来生产人源化糖蛋白以及对蛋白质进行聚糖重塑仍是微生物学家和生物化学家的长期目标,但微生物糖生物学领域的最新研究与合成化学技术相结合表明,这个梦想已接近实现。