Albumin-binding domain from Streptococcus zooepidemicus protein Zag as a novel strategy to improve the half-life of therapeutic proteins

作者：Cantante Catia; Lourenco Sara; Morais Mauricio; Leandro Joao; Gano Lurdes; Silva Nuno; Leandro Paula; Serrano Monica; Henriques Adriano O; Andre Ana; Cunha Santos Catarina; Fontes Carlos; Correia Joao D G; Aires da Silva Frederico^*; Goncalves Joao^*

来源：Journal of Biotechnology, 2017, 253: 23-33.

DOI：10.1016/j.jbiotec.2017.05.017

• Antibody engineering
• Recombinant antibodies
• Half-life extension
• Albumin binding domain
• Streptococcus
• ZAG protein

Recombinant antibody fragments belong to the promising class of biopharmaceuticals with high potential for future therapeutic applications. However, due to their small size they are rapidly cleared from circulation. Binding to serum proteins can be an effective approach to improve pharmacokinetic properties of short half-life molecules. Herein, we have investigated the Zag albumin-binding domain (ABD) derived from Streptococcus zooepidemicus as a novel strategy to improve the pharmacokinetic properties of therapeutic molecules. To validate our approach, the Zag ABD was fused with an anti-TNF alpha single-domain antibody (sdAb). Our results demonstrated that the sdAb-Zag fusion protein was highly expressed and specifically recognizes human, rat and mouse serum albumins with affinities in the nanomolar range. Moreover, data also demonstrated that the sdAb activity against the therapeutic target (TNF alpha) was not affected when fused with Zag ABD. Importantly, the Zag ABD increased the sdAb half-life similar to 39-fold (47 min for sdAb versus 31 h for sdAb-Zag). These findings demonstrate that the Zag ABD fusion is a promising approach to increase the half-life of small recombinant antibodies molecules without affecting their therapeutic efficacy. Moreover, the present study strongly suggests that the Zag ABD fusion strategy can be potentially used as a universal method to improve the pharmokinetics properties of many others therapeutics proteins and peptides in order to improve their dosing schedule and clinical effects.

• 出版日期2017-7-10
• 单位河北医科大学