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脂质体和穿透肽对 10-23 DNA 酶性质影响的研究。

Studies on the Effect of Lipofectamine and Cell-Penetrating Peptide on the Properties of 10-23 DNAzyme.

机构信息

School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, China.

State Key Laboratory of Toxicology and Medical Countermeasurements, Beijing Institute of Pharmacology and Toxicology, Taiping 27, Beijing 100850, China.

出版信息

Molecules. 2023 May 7;28(9):3942. doi: 10.3390/molecules28093942.

Abstract

Cationic polymeric materials and cell-penetrating peptides (CPPs) were often used as the delivery vectors in the evaluation of nucleic acid therapeutics. 10-23 DNAzyme is a kind of potential antisense therapeutics by catalytic cleavage of the disease-related RNAs. Here, lipofectamine 2000 and Tat peptide were evaluated for their effect on the catalytic activity of 10-23 DNAzyme, with the observed rate constant, thermal stability, CD spectra, and PAGE analysis, with a duplex DNA mimicking DNAzyme-substrate as a control. It was shown that the cationic carriers had a negative effect on the catalytic performance of the 10-23 DNAzyme. Significantly, the destabilizing effect of the cationic carriers on the duplex formation was noteworthy, as a duplex formation is an essential prerequisite in the silencing mechanisms of antisense and RNAi.

摘要

阳离子聚合物材料和细胞穿透肽 (CPPs) 常被用作核酸治疗药物评价中的递送载体。10-23 DNA 酶是一种通过催化切割相关 RNA 来发挥作用的潜在反义治疗药物。本文通过观察速率常数、热稳定性、CD 光谱和 PAGE 分析,以双链 DNA 模拟 DNA 酶-底物作为对照,评估了脂质体 2000 和 Tat 肽对 10-23 DNA 酶催化活性的影响。结果表明,阳离子载体对 10-23 DNA 酶的催化性能有负面影响。值得注意的是,阳离子载体对双链形成的去稳定作用非常显著,因为双链形成是反义疗法和 RNAi 沉默机制的必要前提。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f30a/10179765/965710134760/molecules-28-03942-g001.jpg

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