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

Aptamer Conjugated RNA/DNA Hybrid Nanostructures Designed for Efficient Regulation of Blood Coagulation.
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适体缀合 RNA/DNA 混合纳米结构,专为有效调节凝血而设计。

DOI:
10.1007/978-1-0716-3417-2_19
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发表时间:
2023
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
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通讯作者:
Afonin,KirillA
Afonin,KirillA
中科院分区:
--
文献类型:
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作者:
Rolband,LewisA;Ke,Weina;Afonin,KirillA

文献摘要

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止血通路的中断可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护理。凝血酶结合适体是以高特异性和亲和力结合凝血酶的单链核酸。虽然它们可以有效地抑制凝血酶,但它们在体内遭受快速降解和清除。然而,这些问题通过将治疗性适体连接到核酸纳米结构来解决。纳米结构-适体复合物的尺寸增加延长了适体的输注后半衰期。这些复合物也是免疫静止的。使用核酸作为抗凝血剂的一个显着好处是,通过引入完全由治疗活性纳米结构的反向互补物制成的纳米结构,它们可以快速失活。这些优点使得纳米颗粒缀合的抗凝血酶适体成为用于快速可逆的抗凝治疗的有希望的候选物。
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.