Cryo-electron Microscopy of Adeno-associated Virus.
Cryo-electron Microscopy of Adeno-associated Virus.
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DOI：
10.1021/acs.chemrev.1c00936
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发表时间：
2022-09-14
期刊：
影响因子：
62.1
通讯作者：
Chapman, Michael S.
中科院分区：
文献类型：
--
作者：
Stagg, Scott M.;Yoshioka, Craig;Davulcu, Omar;Chapman, Michael S.
腺相关病毒（Adeno-associated virus，AAV）是一种单链DNA病毒，由60个亚单位组成，呈二十面体对称的蛋白质外壳。AAV是新兴的遗传性疾病基因治疗中的领先递送载体，因此其结构和与人类宿主的分子相互作用引起了人们的强烈兴趣。广泛的电子显微镜方法已被用于可视化病毒及其复合物，这取决于科学问题，可用技术和样品的顺从性。方法范围从与大的和灵活的宿主蛋白质的复合物的亚体积层析分析到病毒内原子相互作用的详细分析，以及分辨率高达1.6 μ m的小配体。分析已导致聚糖受体作为附着因子的重新分类、具有新发现的受体蛋白的结构、抗体表位的鉴定以及对可能的中和机制的新理解。AAV现在是足够好的特点，它也已成为EM方法开发的模型系统。预示着一个新时代的到来，cryo-EM现在也被部署为高价值药物生物制剂（即AAV载体）的过程开发和生产质量控制中的分析工具。
Adeno-associated virus (AAV) has a single-stranded DNA genome encapsidated in a small icosahedrally symmetric protein shell with 60 subunits. AAV is the leading delivery vector in emerging gene therapy treatments for inherited disorders, so its structure and molecular interactions with human hosts are of intense interest. A wide array of electron microscopic approaches have been used to visualize the virus and its complexes, depending on the scientific question, technology available, and amenability of the sample. Approaches range from subvolume tomographic analyses of complexes with large and flexible host proteins to detailed analysis of atomic interactions within the virus and with small ligands at resolutions as high as 1.6 Å. Analyses have led to the reclassification of glycan receptors as attachment factors, to structures with a new-found receptor protein, to identification of the epitopes of antibodies, and a new understanding of possible neutralization mechanisms. AAV is now well-enough characterized that it has also become a model system for EM methods development. Heralding a new era, cryo-EM is now also being deployed as an analytic tool in the process development and production quality control of high value pharmaceutical biologics, namely AAV vectors.
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影响因子：
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期刊：
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