Cleaving Folded RNA by Multifunctional DNAzyme Nanomachines

Author:

Nedorezova Daria D.1,Dubovichenko Mikhail V.1,Eldeeb Ahmed A.1,Nur Moustapha A. Y.1,Bobkov Gleb A.1,Ashmarova Anna I.1,Kalnin Arsenij J.1,Kolpashchikov Dmitry M.123ORCID

Affiliation:

1. robotics and biosensor systems and Frontier nucleic acid technologies in gene therapy of cancer SCAMT Institute ITMO University St. Petersburg 191002 Russian Federation

2. Chemistry Department University of Central Florida Orlando FL 32816–2366 USA

3. Burnett School of Biomedical Sciences University of Central Florida Orlando FL 32816

Abstract

AbstractBoth tight and specific binding of folded biological mRNA is required for gene silencing by oligonucleotide gene therapy agents. However, this is fundamentally impossible using the conventional oligonucleotide probes according to the affinity/specificity dilemma. This study addresses this problem for cleaving folded RNA by using multicomponent agents (dubbed ‘DNA nanomachine’ or DNM). DNMs bind RNA by four short RNA binding arms, which ensure tight and highly selective RNA binding. Along with the improved affinity, DNM maintain the high sequence selectivity of the conventional DNAzymes. DNM enabled up to 3‐fold improvement in DNAzymes catalytic efficiency (kcat/Km) by facilitating both RNA substrate binding and product release steps of the catalytic cycle. This study demonstrates that multicomponent probes organized in sophisticated structures can help to achieve the balance between affinity and selectivity in recognizing folded RNA and thus creates a foundation for applying complex DNA nanostructures derived by DNA nanotechnology in gene therapy.

Funder

ITMO University

Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3