Stimuli-Induced Upgrade of Nuclease-Resistant DNA Nanostructure Composed of a Single Molecular Beacon for Detecting Mutant Genes

ACS Sensors ◽  
2021 ◽  
Author(s):  
Chang Xue ◽  
Lei Wang ◽  
Hong Huang ◽  
Ruozhong Wang ◽  
Pei Yuan ◽  
...  
2019 ◽  
Author(s):  
Paul S. Kwon ◽  
Shaokang Ren ◽  
Seok-Joon Kwon ◽  
Megan E. Kizer ◽  
Lili Kuo ◽  
...  

ABSTRACTDNA, when folded into nanostructures of customizable shapes, is capable of spacing and arranging external ligands in a desired geometric pattern with nanometer-precision. This allows DNA to serve as an excellent, biocompatible scaffold for complex spatial pattern-recognizing displays. In this report, we demonstrate that a templated designer DNA nanostructure achieves multi-ligand display with precise spatial pattern-recognition, representing a unique strategy in synthesizing potent viral sensors and inhibitors. Specifically, a star-shaped DNA architecture, carrying five molecular beacon-like motifs, was constructed to display ten dengue virus envelope protein domain-III (ED3)-binding aptamers into a 2D pattern precisely matching the pentagonal arrangement of ED3 clusters on the dengue viral surface. The resulting spatial pattern recognition and multivalent interactions achieve high dengue-binding avidity, conferring direct, highly-sensitive, facile, low-cost, and rapid sensing as well as potent viral inhibition capability. Our molecular-platform design strategy could be adapted to detect and combat other disease-causing pathogens, including bacteria and microbial-toxins, by generating the requisite ligand patterns on customized DNA nanoarchitectures.


Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1617
Author(s):  
Jeonghun Kim ◽  
So Yeon Ahn ◽  
Soong Ho Um

A variety of nanostructured diagnostic tools have been developed for the precise detection of known genetic variants. Molecular beacon systems are very promising tools due to their specific selectivity coupled with relatively lower cost and time requirements than existing molecular detection tools such as next generation sequencing or real-time PCR (polymerase chain reaction). However, they are prone to errors induced by secondary structure responses to environmental fluctuations, such as temperature and pH. Herein, we report a temperature-insensitive, bead-immobilized, molecular beacon-equipped novel DNA nanostructure for detection of cancer miRNA variants with the consideration of thermodynamics. This system consists of three parts: a molecular beacon for cancer-specific RNA capture, a stem body as a core template, and a single bead for solid-support. This DNA system was selectively bound to nanosized beads using avidin–biotin chemistry. Synthetic DNA nanostructures, designed based on the principle of fluorescence-resonance enhanced transfer, were effectively applied for in vitro cancer-specific RNA detection. Several parameters were optimized for higher performance, with a focus on thermodynamic stability. Theoretical issues regarding the secondary structure of a single molecular beacon and its combinatory forms were also studied. This study provides design guidelines for new sensing systems of miRNA variation for next-generation biotechnological applications.


2021 ◽  
Vol 10 (2) ◽  
pp. 319
Author(s):  
Hee Cheol Yang ◽  
Won Jong Rhee

Because cancers are heterogeneous, it is evident that multiplexed detection is required to achieve disease diagnosis with high accuracy and specificity. Extracellular vesicles (EVs) have been a subject of great interest as sources of novel biomarkers for cancer liquid biopsy. However, EVs are nano-sized particles that are difficult to handle; thus, it is necessary to develop a method that enables efficient and straightforward EV biomarker detection. In the present study, we developed a method for single step in situ detection of EV surface proteins and inner miRNAs simultaneously using a flow cytometer. CD63 antibody and molecular beacon-21 were investigated for multiplexed biomarker detection in normal and cancer EVs. A phospholipid-polymer-phospholipid conjugate was introduced to induce clustering of the EVs analyzed using nanoparticle tracking analysis, which enhanced the detection signals. As a result, the method could detect and distinguish cancer cell-derived EVs using a flow cytometer. Thus, single step in situ detection of multiple EV biomarkers using a flow cytometer can be applied as a simple, labor- and time-saving, non-invasive liquid biopsy for the diagnosis of various diseases, including cancer.


Nanoscale ◽  
2021 ◽  
Author(s):  
Jianqin Yan ◽  
Zhuangzhuang Zhang ◽  
xiaohui Zhan ◽  
Keqi Chen ◽  
Yuji Pu ◽  
...  

mproving the deep penetration of nanoparticles and realizing the combination of chemotherapy and immunotherapy have become a promising strategy for cancer treatment. Herein, nuclear-targeted tetrahedral DNA nanostructure (NLS-TDNs, NT) was...


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Brittany S. Ulm ◽  
David R. Borchelt ◽  
Brenda D. Moore

AbstractAlzheimer’s disease (AD) is among the most prevalent neurodegenerative diseases, with brain pathology defined by extracellular amyloid beta deposits and intracellular tau aggregates. To aid in research efforts to improve understanding of this disease, transgenic murine models have been developed that replicate aspects of AD pathology. Familial AD is associated with mutations in the amyloid precursor protein and in the presenilins (associated with amyloidosis); transgenic amyloid models feature one or more of these mutant genes. Recent advances in seeding methods provide a means to alter the morphology of resultant amyloid deposits and the age that pathology develops. In this review, we discuss the variety of factors that influence the seeding of amyloid beta pathology, including the source of seed, the time interval after seeding, the nature of the transgenic host, and the preparation of the seeding inoculum.


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