Liang Fang, Simian Cai, Patrick McMullen, Yi-Chen Hsu, Michelle Yi Qin Chen and Shaoyi Jiang*,
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引用次数: 0
Abstract
Living microbial therapies have been proposed as a course of action for a variety of diseases. However, problematic interactions between the host immune system and the microbial organism present significant clinical concerns. Previously, we developed a genetically encoded superhydrophilic zwitterionic peptide, termed EKP, to mimic low-immunogenic zwitterionic materials, which have been used for the chemical modification of biologics such as protein and nucleic acid drugs to increase their in vivo circulation time and reduce their immunogenicity. Herein, we demonstrate the protective effects of the EKP polypeptide genetically cloaking the surface of Saccharomyces cerevisiae as a model microbe in both in vitro and in vivo systems. First, we show that EKP peptide cloaking suppresses the interactions between yeast cells and their specific antibodies, thereby illustrating its cloaking behavior. Then, we examine the in vitro interactions between EKP peptide surface cloaked yeast cells and murine macrophage cells, which exhibit phagocytotic behavior in the presence of foreign microbes. Our results indicate that EKP cloaking suppresses macrophage interactions and thus reduces phagocytosis. Furthermore, EKP cloaked yeast cells demonstrate a prolonged circulation time in mice in vivo.
活微生物疗法已被提议作为治疗多种疾病的一种方法。然而,宿主免疫系统与微生物有机体之间的相互作用问题给临床带来了极大的困扰。此前,我们开发了一种基因编码的超亲水性齐聚物肽(称为 EKP)来模拟低免疫原性齐聚物,这种齐聚物已被用于对蛋白质和核酸药物等生物制剂进行化学修饰,以延长其体内循环时间并降低其免疫原性。在本文中,我们在体外和体内系统中展示了将 EKP 多肽基因包覆在作为模式微生物的酿酒酵母表面的保护作用。首先,我们发现 EKP 多肽隐形后会抑制酵母细胞与其特异性抗体之间的相互作用,从而说明了它的隐形行为。然后,我们研究了 EKP 肽表面隐形的酵母细胞与小鼠巨噬细胞之间的体外相互作用。我们的研究结果表明,EKP 斗篷会抑制巨噬细胞之间的相互作用,从而减少吞噬作用。此外,EKP 斗篷酵母细胞在小鼠体内的循环时间延长。
期刊介绍:
Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.