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通过 DNA 骨干刷状聚合物提高寡核苷酸的酶稳定性和药代动力学特性。

Improving the Enzymatic Stability and the Pharmacokinetics of Oligonucleotides via DNA-Backboned Bottlebrush Polymers.

机构信息

Department of Chemistry and Chemical Biology , Northeastern University , Boston , Massachusetts 02115 , United States.

出版信息

Nano Lett. 2018 Nov 14;18(11):7378-7382. doi: 10.1021/acs.nanolett.8b03662. Epub 2018 Nov 2.

DOI:10.1021/acs.nanolett.8b03662
PMID:30376347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6571500/
Abstract

Herein, we design and synthesize site-specifically PEGylated oligonucleotide hairpins and demonstrate that their ability to undergo hybridization chain reaction is nearly unaffected by the PEGylation. The resulting DNA-backboned bottlebrush polymers with PEG side chains exhibit increased resistance against nucleolytic degradation, enhanced thermal stabilities, and elevated blood retention times in vivo, which collectively pave the way for more therapeutically focused DNA nanostructure designs.

摘要

在此,我们设计并合成了定点 PEG 化的寡核苷酸发夹,并证明其杂交链式反应能力几乎不受 PEG 化的影响。所得的具有 PEG 侧链的 DNA 骨架刷状聚合物具有更高的抗核酸酶降解能力、增强的热稳定性和体内更长的血液保留时间,这为更具治疗重点的 DNA 纳米结构设计铺平了道路。

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