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作 者:王明蓉[1] 史晋海 何勇智[1] 代云见[1] 余馨[1] 丛聪[1] 何明跃[1]
机构地区:[1]成都生物制品研究所有限责任公司重组药物研究室,610023 [2]Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China
出 处:《国际生物制品学杂志》2016年第5期252-259,共8页International Journal of Biologicals
摘 要:先进的展示技术为重组抗体的筛选和改造提供了有效而灵活的方法.通过展示技术可以获得更适用于诊断和治疗的优化分子,而后者不能直接通过动物免疫接种的方式获得.展示技术可通过自动化或与新一代测序技术和阵列技术联合应用得到进一步提高,形成高通量筛选技术平台,用于筛选多种对应大量基因组编码靶标的抗体.从头设计抗体已开始成为制造新抗体的一种策略,但仍具有技术挑战性.然而,抗体-抗原结构数据库的不断增加和计算工具的不断开发,都表明这些挑战是可以克服的.预计未来以物理分子模拟知识为基础的计算方法,将成为提高抗体设计准确性和成功性的主要驱动力.Advanced display technologies provide powerful and versatile methods for selection and manipulation of recombinant antibodies.They are capable of generating binding molecules with optimised features or properties suitable for diagnostic and therapeutic applications,which may not be achievable by animal immunisation.Potentially,display technologies could be further enhanced by automation or combination with next generation sequencing and array technology,leading to high-throughput platform for selections of multiple antibodies against a wide range of genome-coded targets.De novo design of antibodies is becoming an alternative for developing novel antibodies,though technical challenges are still present.However,the continuously increasing databases of antibody-antigen structures and the advances in the development of computational tools suggest that these challenges can be overcome.Knowledge based computational methods with physics-based molecular simulations are expected to become the main drivers in future to improve the accuracy and success of the design.
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