Cry protein crystals: a novel platform for protein delivery.

Cry protein crystals: a novel platform for protein delivery.
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DOI:
10.1371/journal.pone.0127669
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Chan MK
Chan MK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nair MS;Lee MM;Bonnegarde-Bernard A;Wallace JA;Dean DH;Ostrowski MC;Burry RW;Boyaka PN;Chan MK

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蛋白质传递平台是开发新型蛋白质疗法和生物技术的重要工具。我们已经开发了一种基于亚微米大小的Cry3Aa蛋白晶体的新型蛋白质递送剂,这种晶体在苏云金芽孢杆菌中自然形成。我们证明了cry3Aa基因与各种报告蛋白的融合可以方便地生产用于后续应用的cry3Aa融合蛋白晶体。这些Cry3Aa融合蛋白晶体在体外被巨噬细胞和其他细胞系有效地吸收和保留,并可通过多种给药方式在体内给药。将Cry3Aa融合蛋白晶体口服给C57BL/6小鼠,可导致其被MHC II类细胞(包括Peyer’s patches中的巨噬细胞)摄取,这支持了Cry3Aa框架可用于稳定货物蛋白以防止降解递送到胃肠道淋巴组织的观点。
Protein delivery platforms are important tools in the development of novel protein therapeutics and biotechnologies. We have developed a new class of protein delivery agent based on sub-micrometer-sized Cry3Aa protein crystals that naturally form within the bacterium Bacillus thuringiensis. We demonstrate that fusion of the cry3Aa gene to that of various reporter proteins allows for the facile production of Cry3Aa fusion protein crystals for use in subsequent applications. These Cry3Aa fusion protein crystals are efficiently taken up and retained by macrophages and other cell lines in vitro, and can be delivered to mice in vivo via multiple modes of administration. Oral delivery of Cry3Aa fusion protein crystals to C57BL/6 mice leads to their uptake by MHC class II cells, including macrophages in the Peyer’s patches, supporting the notion that the Cry3Aa framework can be used to stabilize cargo protein against degradation for delivery to gastrointestinal lymphoid tissues.
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