Delivery of Superoxide Dismutase Using Cys2-His2 Zinc--Finger Proteins

Delivery of Superoxide Dismutase Using Cys2-His2 Zinc--Finger Proteins
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使用 Cys2-His2 锌指蛋白递送超氧化物歧化酶。

DOI:
10.1007/978-1-4939-8799-3_9
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发表时间:
2018-01-01
期刊:
ZINC FINGER PROTEINS: METHODS AND PROTOCOLS
影响因子:
--
通讯作者:
Ma, Peixiang
Ma, Peixiang
中科院分区:
其他
文献类型:
--
作者:
Liu, Jia;Li, Jiangmei;Ma, Peixiang

文献摘要

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治疗性蛋白在治疗危及生命的疾病方面显示出巨大的潜力,但其亲水性和高分子量阻碍了它们通过细胞膜。细胞穿透肽(CPP)辅助的蛋白质递送是促进细胞摄取治疗性蛋白质的一种简单而有效的策略。我们最近证明了设计的Cys2-His2锌指结构域具有内在的细胞通透性,这可以用于细胞内蛋白质的传递。在这里,我们应用这种方法来传递超氧化物歧化酶(SOD),这是一种广泛用于临床前和临床研究的治疗性蛋白质。我们提出了一种生产和递送锌指结构域融合超氧化物歧化酶的方法。这一方案可以扩展到输送其他治疗性蛋白。
Therapeutic proteins have shown great potential in treating life-threatening diseases, but the hydrophilicity and high molecular weight hamper their passing through the cell membrane. Cell-penetrating peptide (CPP)-assisted protein delivery is a simple and efficacious strategy to promote the cellular uptake of therapeutic proteins. We recently demonstrated that the engineered Cys2-His2zinc-finger domains possess intrinsic cell permeability, which could be leveraged for intracellular protein delivery. Here we applied this method to deliver superoxide dismutase (SOD), a therapeutic protein widely used in preclinical and clinical studies. We present a protocol for the production and delivery of zinc-finger domain-fused SOD. This protocol can be extended for delivering other therapeutic proteins.