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开发基于肉毒神经毒素的可插入和输送的细胞内蛋白质输送平台

Seong Guk Park¹, Hyun Bin Lee¹, Sebyung Kang¹

¹Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

International journal of biological macromolecules

|January 24, 2024

概括

我们开发了一种基于A型肉毒神经毒素 (BoNT/A) 的新型系统,用于向细胞内蛋白质的输送. 这个平台有效地将蛋白质载荷送入细胞,克服了治疗开发的主要输送挑战.

科学领域:

生物技术是生物技术.
分子生物学分子生物学
细胞工程细胞工程

背景情况:

细胞内蛋白质的输送对于治疗和研究至关重要.
关键的挑战包括有针对性的分娩,非破坏性的细胞进入和内体体逃生.

研究的目的:

开发一种新的,模块化的,针对特定目标的细胞内蛋白质输送系统.
为增强蛋白质货物交付设计基于A型肉毒神经毒素 (BoNT/A) 的平台.

主要方法:

经过基因工程改造的BoNT/A衍生模块 (LHNA) 与SpyCatcher (SC) 融合,以及一个针对EGFR的附属体 (EGFRAfb).
净化了SC-LHNA-EGFRAfb结构,并将其与蛋白质货物结合起来.
通过受体介导内细胞和内体逃逸,通过受体介导内细胞和内体逃逸,评估输送效率到细胞.

主要成果:

成功创建了一个可切换的基于BoNT/A的交付平台 (SC-LHNA-EGFRAfb).
证明了绑定蛋白质货物的有效细胞质输送.
在凝的细胞内传递中实现了100倍的增强,突出了EGFRAfb和LHNA的作用.

结论:

基于BoNT/A的系统是针对细胞内蛋白质的有希望的工具.
这个平台促进了蛋白质疗法开发和细胞过程操纵.
模块化设计允许多功能货物装载和特定准.

关键词:

肉毒神经毒素是一种神经毒素.细胞内蛋白质的输送.有针对性的交付目标.

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