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DNA is the primary genetic material that is highly compatible with biological system, and its intrinsic property of complementary base pairing can be programmed for analysis. However, single-stranded DNA probes present challenges as they are difficult to internalize into cells and can easily decompose in the cell microenvironment. In recent years, the development of framework nucleic acids (FNAs) has enabled DNA nanostructures to emerge as promising materials for bioimaging, drug delivery, and biosensor design. These probes offer several advantages, including high biological stability, efficient cell internalization, low dynamic limitations, and diverse signal output. Therefore, it is important to review and summarize the critical role of framework design in DNA-based biosensor construction for the advancement of DNA nanotechnology and its application in bioanalysis. This article provides an overview of the development and limitations of DNA nanostructures in different dimensions and highlights the endocytosis of tetrahedral DNA frameworks (TDF) and their applications in biosensing and imaging. Finally, existing signal output modes are introduced to provide a comprehensive understanding of the potential applications of TDF. [Display omitted] • A comprehensive review on the structure and performance of tetrahedral DNA frameworks (TDF) is reported. • Different intracellular targets detected by TDF-based probes are discussed. • Multiple signal output modes using TDF are summarized. • The challenges and clinical barriers of TDF are also listed. [ABSTRACT FROM AUTHOR]

Identification of tumor-related mRNA in living cells hold great promise for early cancer diagnosis and pathological research. Herein, we present poly-adenine (polyA)-mediated fluorescent spherical nucleic acid (FSNA) probes for intracellular mRNA detection with regulable sensitivities by programmably adjusting the loading density of DNA on gold nano-interface. Gold nanoparticles (AuNPs) functionalized with polyA-tailed recognition sequences were hybridized to fluorescent “reporter” strands to fabricate fluorescence-quenched FSNA probes. While exposed to target gene, the “reporter” strands were released from FSNA through strand displacement and fluorescence was recovered. With polyA20 tail as the attaching block, the detection limit of FSNA probes was calculated to be 0.31 nM, which is ~55 fold lower than that of thiolated probes without surface density regulation. Quantitative intracellular mRNA detection and imaging could be achieved with polyA-mediated FSNA probes within 2 hours, indicating their application potential in rapid and sensitive intracellular target imaging. [ABSTRACT FROM AUTHOR]

Mercury (II) ion (Hg 2+ ) contamination can be accumulated along the food chain and cause serious threat to the public health. Plenty of research effort thus has been devoted to the development of fast, sensitive and selective biosensors for monitoring Hg 2+ . Thymine was demonstrated to specifically combine with Hg 2+ and form a thymine–Hg 2+ –thymine (T–Hg 2+ –T) structure, with binding constant even higher than T-A Watson-Crick pair in DNA duplex. Recently, various novel Hg 2+ biosensors have been developed based on T-rich Mercury-Specific Oligonucleotide (MSO) probes, and exhibited advanced selectivity and excellent sensitivity for Hg 2+ detection. In this review, we explained recent development of MSO-based Hg 2+ biosensors mainly in 3 groups: fluorescent biosensors, colorimetric biosensors and electrochemical biosensors. [ABSTRACT FROM AUTHOR]

Electrochemical DNA (E-DNA) sensor is an important tool for detecting DNA biomarker. In this work, we have demonstrated a novel strategy of E-DNA sensor based on DNA tetrahedral nanostructures for the sensitive detection of target DNA. In our design, thiol and biotin modified DNA tetrahedral nanostructures were used as capture and report probes respectively. The biotin-tagged three dimensional DNA tetrahedral nanostructures were employed for efficient signal amplification by capturing multiple catalytic enzymes. Such improved E-DNA sensor can sensitively detect DNA target as low as 1 fM with excellent differentiation ability for even single mismatch. And a mean recovery rate of 90.57% in DNA solution extracted from human serum was obtained. We have also compared this new method of attaching catalytic enzymes with the other two typical methods: One is through biotinylated single-stranded DNA (SSDNA) and the other is through gold nanoparticles (GNPs). Results indicated that the RTSPs-based enzyme amplification system showed much better performance than the other two systems. [ABSTRACT FROM AUTHOR]

The development of sensitive telomerase biosensors is hindered by the restricted accessibility of telomere strand (TS) primer and the limited enzyme reaction space, which is mainly confined by the vertical distance. In this work, we designed an electrochemical telomerase biosensor based on a spired DNA tetrahedron TS primer (STTS). By adding a rigid dsDNA spire onto the top of the DNA tetrahedron, we successfully regulated the distance between the TS primer and the surface, and thus greatly facilitated the telomerase elongation on surface. The signal-to-noise ratio was 2 times higher than TSP without the spire structure. The limit of detection was calculated to be lower than 10 HeLa cells, which is at least 2 magnitudes lower than other surface extension-based electrochemical telomerase sensors without amplification. The practicability of STTS sensor was also demonstrated by analysing various other cell lines including cancer cells, stem cells of high telomerase activity and somatic cells of low telomerase activity. [ABSTRACT FROM AUTHOR]

Abstract: Here, we have demonstrated an ultra-high sensitive detection platform with the detection limit of 5pM for an environmental toxin—Pb2+. We designed a Pb2+ triggered exonuclease aided DNA recycling system to improve the detection sensitivity. In our system, a Pb2+ dependent 8–17 DNAzyme and its substrate were used to form hybridization duplex. In the presence of Pb2+, the substrate was cleaved and disassociated from the duplex. Then, the released 8–17 DNAzyme was used as a target of the exonuclease aided DNA recycling system which can amplify the fluorescence signal by recycling the 8–17 DNAzyme continuously. Then, the sensitive Pb2+ detection are accomplished and the detection limit of Pb2+ was down to 5pM which is about 1000 times lower than the traditional detection method based on the 8–17 DNAzyme. [Copyright &y& Elsevier]