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一种有前景的核酸治疗药物:脱氧核酶及其递送系统。

A promising nucleic acid therapy drug: DNAzymes and its delivery system.

作者信息

Xiao Lang, Zhao Yan, Yang Meng, Luan Guangxin, Du Ting, Deng Shanshan, Jia Xu

机构信息

School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China.

Sichuan Key Laboratory of Noncoding RNA and Drugs, Chengdu Medical College, Chengdu, Sichuan, China.

出版信息

Front Mol Biosci. 2023 Sep 11;10:1270101. doi: 10.3389/fmolb.2023.1270101. eCollection 2023.

DOI:10.3389/fmolb.2023.1270101
PMID:37753371
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10518456/
Abstract

Based on the development of nucleic acid therapeutic drugs, DNAzymes obtained through selection technology in 1994 are gradually being sought. DNAzymes are single-stranded DNA molecules with catalytic function, which specifically cleave RNA under the action of metal ions. Various and models have recently demonstrated that DNAzymes can target related genes in cancer, cardiovascular disease, bacterial and viral infection, and central nervous system disease. Compared with other nucleic acid therapy drugs, DNAzymes have gained more attention due to their excellent cutting efficiency, high stability, and low cost. Here, We first briefly reviewed the development and characteristics of DNAzymes, then discussed disease-targeting inhibition model of DNAzymes, hoping to provide new insights and ways for disease treatment. Finally, DNAzymes were still subject to some restrictions in practical applications, including low cell uptake efficiency, nuclease degradation and interference from other biological matrices. We discussed the latest delivery strategy of DNAzymes, among which lipid nanoparticles have recently received widespread attention due to the successful delivery of the COVID-19 mRNA vaccine, which provides the possibility for the subsequent clinical application of DNAzymes. In addition, the future development of DNAzymes was prospected.

摘要

基于核酸治疗药物的发展,1994年通过筛选技术获得的脱氧核酶正逐渐受到关注。脱氧核酶是具有催化功能的单链DNA分子,在金属离子作用下能特异性切割RNA。最近的各种模型表明,脱氧核酶可靶向癌症、心血管疾病、细菌和病毒感染以及中枢神经系统疾病中的相关基因。与其他核酸治疗药物相比,脱氧核酶因其出色的切割效率、高稳定性和低成本而受到更多关注。在此,我们首先简要回顾了脱氧核酶的发展历程和特点,然后讨论了脱氧核酶的疾病靶向抑制模型,希望能为疾病治疗提供新的见解和方法。最后,脱氧核酶在实际应用中仍受到一些限制,包括细胞摄取效率低、核酸酶降解以及来自其他生物基质的干扰。我们讨论了脱氧核酶的最新递送策略,其中脂质纳米颗粒由于成功递送了新冠mRNA疫苗而最近受到广泛关注,这为脱氧核酶的后续临床应用提供了可能性。此外,还对脱氧核酶的未来发展进行了展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ff0/10518456/04719c4653a9/fmolb-10-1270101-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ff0/10518456/ec22952a2b30/fmolb-10-1270101-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ff0/10518456/e87633c1e1e7/fmolb-10-1270101-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ff0/10518456/04719c4653a9/fmolb-10-1270101-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ff0/10518456/ec22952a2b30/fmolb-10-1270101-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ff0/10518456/e87633c1e1e7/fmolb-10-1270101-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ff0/10518456/04719c4653a9/fmolb-10-1270101-g003.jpg

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本文引用的文献

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A dynamic DNA nanosponge for triggered amplification of gene-photodynamic modulation.一种用于触发基因光动力调节扩增的动态DNA纳米海绵。
Chem Sci. 2022 Mar 28;13(18):5155-5163. doi: 10.1039/d2sc00459c. eCollection 2022 May 11.
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Nucleic Acids and Their Analogues for Biomedical Applications.核酸及其类似物在生物医学中的应用。
Molecules. 2024 Oct 23;29(21):5011. doi: 10.3390/molecules29215011.
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Multivalent DNAzyme agents for cleaving folded RNA.多价 DNA 酶试剂用于切割折叠 RNA。
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Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs.三种已获批的 siRNA(Patisiran)和 mRNA(COVID-19 疫苗)药物中所采用的脂质纳米颗粒技术的差异。
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mRNA vaccines for infectious diseases: principles, delivery and clinical translation.传染病的 mRNA 疫苗:原理、传递和临床转化。
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Biosensing with DNAzymes.DNA 酶的生物传感。
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