抗肉毒毒素纳米抗体的研究进展  

Nanobodies against botulinum neurotoxins:research progress

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作  者:吕若梅 王菁 辛文文 康琳 宋玉竹[1] Lü Ruo-mei;WANG Jing;XIN Wen-wen;KANG Lin;SONG Yu-zhu(Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming 650500,China;State Key Laboratory of Pathogen and Biosecurity,Institute of Microbiology and Epidemiology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100071,China)

机构地区:[1]昆明理工大学生命科学与技术学院,昆明650500 [2]军事科学院军事医学研究院微生物流行病研究所,病原微生物生物安全国家重点实验室,北京100071

出  处:《军事医学》2022年第11期872-876,F0003,共6页Military Medical Sciences

基  金:病原微生物生物安全国家重点实验室自主研究项目(SKLPBS2113)。

摘  要:肉毒中毒是由于人体摄入肉毒毒素引起的,发病迅速且死亡率很高。目前肉毒中毒的治疗以马血清抗毒素为主,也有多种新型基因工程抗体药物在研,纳米抗体便是其中之一。纳米抗体是近年来的研究热点,具有相对分子质量小、稳定性好、亲和力高及易生产改造等特点,多项研究报道抗肉毒毒素纳米抗体具有良好的中和效果。纳米抗体用于临床治疗的主要问题是半衰期太短,目前延长纳米抗体半衰期的方法包括偶联聚乙二醇(PEG)、利用红细胞载体、融合免疫球蛋白G的Fc段及人血清白蛋白(HSA)等。该文对肉毒毒素纳米抗体的筛选、表达及改造方法进行了综述,为后续肉毒毒素纳米抗体的研究提供参考。Botulism is caused by the ingestion of botulism neurotoxin,with rapid disease onset and potentially high mortality. Botulism is mainly treated with equine derived botulinum antitoxin. Recently,many new genetic engineering antibody medicines are also used to cure botulism,such as nanobodies,which are becoming increasingly popular as reagents for biomedical research for therapeutic use in recent years,characterized by a small relative molecular mass,good stability,high antigen affinity and easy production and transformation. A number of studies have reported the outstanding neutralizing effect of anti-botulinum toxin nanobodies. However,the main disadvantage of nanobodies in clinical treatment is its short half-life period,so many studies have focused on prolonging the half-life of nanobodies,including polyethylene glycol(PEG)conjugation,coupling to red blood cell carriers,fusing with the Fc segment of immunoglobulin G and HSA protein. This article reviews the screening,preparation,and modification methods of nanobodies against botulinum neurotoxins,which can provide support for subsequent research on botulinum neurotoxin nanobodies.

关 键 词:纳米抗体 单域抗体 肉毒毒素 半衰期 异二聚体 

分 类 号:R996.1[医药卫生—毒理学]

 

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