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适体偶联 RNA/DNA 杂交纳米结构设计用于高效调节血液凝固。

Aptamer Conjugated RNA/DNA Hybrid Nanostructures Designed for Efficient Regulation of Blood Coagulation.

机构信息

University of North Carolina at Charlotte, Charlotte, NC, USA.

出版信息

Methods Mol Biol. 2023;2709:277-286. doi: 10.1007/978-1-0716-3417-2_19.

Abstract

Disruptions to the hemostatic pathway can cause a variety of serious or even life-threatening complications. Situations in which the coagulation of blood has become disturbed necessitate immediate care. Thrombin-binding aptamers are single-stranded nucleic acids that bind to thrombin with high specificity and affinity. While they can effectively inhibit thrombin, they suffer from rapid degradation and clearance in vivo. These issues are resolved, however, by attaching the therapeutic aptamer to a nucleic acid nanostructure. The increased size of the nanostructure-aptamer complex elongates the post-infusion half-life of the aptamer. These complexes are also immunoquiescent. A significant benefit of using nucleic acids as anticoagulants is their rapid deactivation by the introduction of a nanostructure made fully from the reverse complement of the therapeutically active nanostructure. These advantages make nanoparticle conjugated antithrombin aptamers a promising candidate for a rapidly reversible anticoagulant therapy.

摘要

止血途径的紊乱会导致各种严重甚至危及生命的并发症。血液凝固受到干扰的情况需要立即进行护理。凝血酶结合适体是与凝血酶具有高特异性和亲和力的单链核酸。虽然它们可以有效地抑制凝血酶,但它们在体内会迅速降解和清除。然而,通过将治疗适体连接到核酸纳米结构上,可以解决这些问题。纳米结构-适体复合物的增大延长了适体输注后的半衰期。这些复合物也是免疫惰性的。使用核酸作为抗凝剂的一个显著优势是,通过引入完全由治疗有效纳米结构的反向互补组成的纳米结构,可以迅速使核酸失活。这些优势使得纳米颗粒共轭抗凝血酶适体成为一种有前途的快速可逆抗凝治疗候选物。

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Micellar Thrombin-Binding Aptamers: Reversible Nanoscale Anticoagulants.胶束凝血酶结合适体:可逆纳米抗凝剂。
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本文引用的文献

1
Aptamers Regulating the Hemostasis System.适配子调控止血系统。
Molecules. 2022 Dec 6;27(23):8593. doi: 10.3390/molecules27238593.
7
Modulation of the Coagulation Cascade Using Aptamers.使用适配体调节凝血级联反应。
Arterioscler Thromb Vasc Biol. 2015 Oct;35(10):2083-91. doi: 10.1161/ATVBAHA.115.300131. Epub 2015 Aug 27.
9
Multifunctional RNA nanoparticles.多功能RNA纳米颗粒
Nano Lett. 2014 Oct 8;14(10):5662-71. doi: 10.1021/nl502385k. Epub 2014 Sep 30.

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