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酶法合成周期性 DNA 纳米带用于细胞内 pH 传感和基因沉默。

Enzymatic synthesis of periodic DNA nanoribbons for intracellular pH sensing and gene silencing.

机构信息

Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, United States.

出版信息

J Am Chem Soc. 2015 Mar 25;137(11):3844-51. doi: 10.1021/ja512665z. Epub 2015 Feb 5.

DOI:10.1021/ja512665z
PMID:25622178
Abstract

We report the construction of periodic DNA nanoribbons (DNRs) by a modified DNA origami method. Unlike the conventional DNA origami, the DNR scaffold is a long, single-stranded DNA of tandem repeats, originating from the rolling circular amplification (RCA). Consequently, the number of folding staple strands tremendously decreases from hundreds to a few, which makes the DNR production scalable and cost-effective, thus potentially removing the barrier for practical applications of DNA nanostructures. Moreover, the co-replicational synthesis of scaffold and staple strands by RCA-based enzymatic reactions allows the generation of DNRs in one pot, further reducing the cost. Due to their unique periodicity, rigidity, and high aspect ratio, DNRs are efficiently internalized into cells and escape from endosomal entrapment, making them potential nanocarriers for imaging agents and biological therapeutics. We demonstrated proof-of-concept applications of DNRs as an intracellular pH sensor and an efficient small interfering RNA delivery vehicle in human cancer cells.

摘要

我们报告了通过改良的 DNA 折纸方法构建周期性 DNA 纳米带 (DNR)。与传统的 DNA 折纸不同,DNR 支架是来自滚环扩增 (RCA) 的串联重复的长单链 DNA。因此,折叠的订书钉链的数量从数百个急剧减少到几个,这使得 DNR 的生产具有可扩展性和成本效益,从而有可能消除 DNA 纳米结构实际应用的障碍。此外,基于 RCA 的酶反应的支架和订书钉链的共复制合成允许在一个锅中生成 DNR,进一步降低成本。由于其独特的周期性、刚性和高纵横比,DNR 有效地被内化到细胞中并逃脱内体捕获,使它们成为成像剂和生物治疗剂的潜在纳米载体。我们证明了 DNR 作为细胞内 pH 传感器和人癌细胞中有效小干扰 RNA 递送载体的概念验证应用。

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