Real-time observation of protein aggregates in pharmaceutical formulations using liquid cell electron microscopy
Real-time observation of protein aggregates in pharmaceutical formulations using liquid cell electron microscopy
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DOI：
10.1039/c6lc01160h
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发表时间：
2017-01-21
期刊：
影响因子：
6.1
通讯作者：
Kelly, Deborah F.
中科院分区：
文献类型：
--
作者：
DiMemmo, Lynn M.;Varano, A. Cameron;Kelly, Deborah F.
了解基于蛋白质的治疗方法的特性是生物学家和医生的共同目标。直接观察小蛋白或治疗剂的技术障碍可能会限制我们对它们在溶液和体内如何发挥作用的了解。在液体环境中进行的电子显微镜（EM）成像使我们能够在纳米级上窥视细胞和分子的活跃世界。在这里，我们采用液体细胞EM以时间分辨的方式直接可视化天然构象和聚集状态的蛋白质基治疗剂。结合定量分析，这项工作的信息为理解模拟人体的溶液状态下免疫疗法的行为提供了新的分子见解。
Understanding the properties of protein-based therapeutics is a common goal of biologists and physicians. Technical barriers in the direct observation of small proteins or therapeutic agents can limit our knowledge of how they function in solution and in the body. Electron microscopy (EM) imaging performed in a liquid environment permits us to peer into the active world of cells and molecules at the nanoscale. Here, we employ liquid cell EM to directly visualize a protein-based therapeutic in its native conformation and aggregate state in a time-resolved manner. In combination with quantitative analyses, information from this work contributes new molecular insights toward understanding the behaviours of immunotherapies in a solution state that mimics the human body.