scholarly journals Spatiotemporally programmable cascade hybridization of hairpin DNA in polymeric nanoframework for precise siRNA delivery

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Li ◽  
Wenting Yu ◽  
Jiaojiao Zhang ◽  
Yuhang Dong ◽  
Xiaohui Ding ◽  
...  

AbstractDNA nanostructures have been demonstrated as promising carriers for gene delivery. In the carrier design, spatiotemporally programmable assembly of DNA under nanoconfinement is important but has proven highly challenging due to the complexity–scalability–error of DNA. Herein, a DNA nanotechnology-based strategy via the cascade hybridization chain reaction (HCR) of DNA hairpins in polymeric nanoframework has been developed to achieve spatiotemporally programmable assembly of DNA under nanoconfinement for precise siRNA delivery. The nanoframework is prepared via precipitation polymerization with Acrydite-DNA as cross-linker. The potential energy stored in the loops of DNA hairpins can overcome the steric effect in the nanoframework, which can help initiate cascade HCR of DNA hairpins and achieve efficient siRNA loading. The designer tethering sequence between DNA and RNA guarantees a triphosadenine triggered siRNA release specifically in cellular cytoplasm. Nanoframework provides stability and ease of functionalization, which helps address the complexity–scalability–error of DNA. It is exemplified that the phenylboronate installation on nanoframework enhanced cellular uptake and smoothed the lysosomal escape. Cellular results show that the siRNA loaded nanoframework down-regulated the levels of relevant mRNA and protein. In vivo experiments show significant therapeutic efficacy of using siPLK1 loaded nanoframework to suppress tumor growth.

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Jaimie Marie Stewart ◽  
Elisa Franco

AbstractNucleic acid nanotechnology offers many methods to build self-assembled structures using RNA and DNA. These scaffolds are valuable in multiple applications, such as sensing, drug delivery and nanofabrication. Although RNA and DNA are similar molecules, they also have unique chemical and structural properties. RNA is generally less stable than DNA, but it folds into a variety of tertiary motifs that can be used to produce complex and functional nanostructures. Another advantage of using RNA over DNA is its ability to be encoded into genes and to be expressed in vivo. Here we review existing approaches for the self-assembly of RNA and DNA nanostructures and specifically methods to assemble large RNA structures. We describe de novo design approaches used in DNA nanotechnology that can be ported to RNA. Lastly, we discuss some of the challenges yet to be solved to build micron-scale, multi stranded RNA scaffolds.


2013 ◽  
Vol 783 ◽  
pp. 17-23 ◽  
Author(s):  
Junyang Zhuang ◽  
Libing Fu ◽  
Mingdi Xu ◽  
Huanghao Yang ◽  
Guonan Chen ◽  
...  

2017 ◽  
Vol 53 (96) ◽  
pp. 12878-12881 ◽  
Author(s):  
Jing Wang ◽  
Min Pan ◽  
Jie Wei ◽  
Xiaoqing Liu ◽  
Fuan Wang

The amplified and selective detection of uracil-DNA glycosylase was enabled by a two-layered cascaded hybridization chain reaction machinery.


2020 ◽  
Vol 11 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Han Wu ◽  
Ting-Ting Chen ◽  
Xiang-Nan Wang ◽  
Yonggang Ke ◽  
Jian-Hui Jiang

Using an in vivo hybridization chain reaction with a tripartite DNA probe to image RNA in living mice may open the door for intracellular RNA imaging in living mammalian animals, implying its potential for tumor biology studies and theranostics.


2020 ◽  
Vol 48 (10) ◽  
pp. e60-e60 ◽  
Author(s):  
Jie Wei ◽  
Huimin Wang ◽  
Xue Gong ◽  
Qing Wang ◽  
Hong Wang ◽  
...  

Abstract The construction of robust, modular and compact DNA machinery facilitates us to build more intelligent and ingenious sensing strategies in complex biological systems. However, the performance of conventional DNA amplifiers is always impeded by their limited in-depth amplifications and miscellaneously enzymatic requirements. Here, a proteinase-free reciprocal DNA replication machinery is developed by exploiting the synergistic cross-activation between hybridization chain reaction (HCR) and DNAzyme. The DNAzyme provides an efficient way to simplify the sophisticated design of HCR machinery and simultaneously to promote the amplification capacity. And the HCR-assembled tandem DNAzyme nanowires produce numerous new triggers for reversely stimulating HCR amplifier as systematically explored by experiments and computer-aided simulations. The reciprocal amplifier can be executed as a versatile and powerful sensing platform for analyzing miRNA in living cells and even in mice, originating from the inherent reaction accelerations and multiple-guaranteed recognitions. The reciprocal catalytic DNA machine holds great potential in clinical diagnosis and assessment.


2020 ◽  
Vol 56 (49) ◽  
pp. 6668-6671
Author(s):  
Meng-Mei Lv ◽  
Zhan Wu ◽  
Ru-Qin Yu ◽  
Jian-Hui Jiang

A well-defined 3D DNA nanostructure was developed by combination of DNA tetrahedron and Y-shaped DNA, which allowed multiplexed, signal amplified fluorescent imaging of miRNAs in living cells via hybridization chain reaction.


2019 ◽  
Vol 10 (42) ◽  
pp. 9758-9767 ◽  
Author(s):  
Jing Wang ◽  
Dong-Xia Wang ◽  
Jia-Yi Ma ◽  
Ya-Xin Wang ◽  
De-Ming Kong

Nonenzymatic nucleic acid amplification techniques (e.g. the hybridization chain reaction, HCR) have shown promising potential for amplified detection of biomarkers.


2020 ◽  
Vol 48 (5) ◽  
pp. 2220-2231 ◽  
Author(s):  
Shaofei Li ◽  
Pan Li ◽  
Meihong Ge ◽  
Hongzhi Wang ◽  
Yizhuang Cheng ◽  
...  

Abstract Hybridization chain reaction (HCR) was a significant discovery for the development of nanoscale materials and devices. One key challenge for HCR is the vulnerability to background leakage in the absence of the initiator. Here, we systematically analyze the sources of leakage and refine leak-resistant rule by using molecular thermodynamics and dynamics, biochemical and biophysical methods. Transient melting of DNA hairpin is revealed to be the underlying cause of leakage and that this can be mitigated through careful consideration of the sequence thermodynamics. The transition threshold of the energy barrier is proposed as a testing benchmark of leak-resistance DNA hairpins. The universal design of DNA hairpins is illustrated by the analysis of hsa-miR-21-5p as biomarker when used in conjunction with surface-enhanced Raman spectroscopy. We further extend the strategy for specific signal amplification of miRNA homologs. Significantly, it possibly provides a practical route to improve the accuracy of DNA self-assembly for signal amplification, and that could facilitate the development of sensors for the sensitive detection of interest molecules in biotechnology and clinical medicine.


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