Super large proteinaceous particles (SLPPs) such as virus, virus like particles, and extracellular vesicles have successful and promising applications in vaccination, gene therapy, and cancer treatment. The unstable nature, the complex particulate structure and composition are challenges for their manufacturing and applications. Rational design of the processing should be built on the basis of fully understanding the characteristics of these bio‐particles. This review highlights useful analytical techniques for characterization and stabilization of SLPPs in the process development and product formulations, including high performance size exclusion chromatography, multi‐angle laser light scattering, asymmetrical flow field‐flow fractionation, nanoparticle tracking analysis, CZE, differential scanning calorimetry, differential scanning fluorescence, isothermal titration calorimetry , and dual polarization interferometry. These advanced analytical techniques will be helpful in obtaining deep insight into the mechanism related to denaturation of SLPPs, and more importantly, in seeking solutions to preserve their biological functions against deactivation or denaturation. Combination of different physicochemical techniques, and correlation with in vitro or in vivo biological activity analyses, are considered to be the future trend of development in order to guarantee a high quality, safety, and efficacy of SLPPs.

中文翻译：

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超大蛋白质颗粒的工艺开发和产品配方的表征和稳定


病毒、病毒样颗粒和细胞外囊泡等超大蛋白质颗粒（SLPP）在疫苗接种、基因治疗和癌症治疗中具有成功且有前景的应用。不稳定的性质、复杂的颗粒结构和成分对其制造和应用提出了挑战。合理的工艺设计应建立在充分了解这些生物颗粒特性的基础上。本综述重点介绍了在工艺开发和产品配方中用于表征和稳定 SLPP 的有用分析技术，包括高性能尺寸排阻色谱、多角度激光光散射、不对称流场流分级分离、纳米颗粒跟踪分析、CZE、差示扫描量热法、差示扫描荧光、等温滴定量热法和双偏振干涉法。这些先进的分析技术将有助于深入了解SLPP变性的相关机制，更重要的是，有助于寻求保护其生物功能免遭失活或变性的解决方案。不同理化技术的结合以及与体外或体内生物活性分析的相关性被认为是未来发展的趋势，以保证SLPP的高质量、安全性和有效性。