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Biosensors Aug 2023Virus-related infectious diseases are serious threats to humans, which makes virus detection of great importance. Traditional virus-detection methods usually suffer from... (Review)
Review
Virus-related infectious diseases are serious threats to humans, which makes virus detection of great importance. Traditional virus-detection methods usually suffer from low sensitivity and specificity, are time-consuming, have a high cost, etc. Recently, DNA biosensors based on DNA nanotechnology have shown great potential in virus detection. DNA nanotechnology, specifically DNA tiles and DNA aptamers, has achieved atomic precision in nanostructure construction. Exploiting the programmable nature of DNA nanostructures, researchers have developed DNA nanobiosensors that outperform traditional virus-detection methods. This paper reviews the history of DNA tiles and DNA aptamers, and it briefly describes the Baltimore classification of virology. Moreover, the advance of virus detection by using DNA nanobiosensors is discussed in detail and compared with traditional virus-detection methods. Finally, challenges faced by DNA nanobiosensors in virus detection are summarized, and a perspective on the future development of DNA nanobiosensors in virus detection is also provided.
Topics: Humans; Aptamers, Nucleotide; Nanotechnology; Nanostructures; DNA
PubMed: 37622908
DOI: 10.3390/bios13080822 -
Blood Nov 2023Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant adult-onset disorder caused by point mutations in the transthyretin (TTR) gene encoding TTR,...
Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant adult-onset disorder caused by point mutations in the transthyretin (TTR) gene encoding TTR, also known as prealbumin. ATTRv survival ranges from 3 to 10 years, and peripheral nervous system and heart are usually the 2 main tissues affected, although central nervous system and eye may also be involved. Because the liver is the main TTR protein secretor organ, it has been the main target of treatments developed these last years, including liver transplantation, which has been shown to significantly increase survival in a subset of patients carrying the so-called "early-onset Val30Met" TTR gene mutation. More recently, treatments targeting hepatic TTR RNA have been developed. Hepatic TTR RNA targeting is performed using RNA interference (RNAi) and antisense oligonucleotide (ASO) technologies involving lipid nanoparticle carriers or N-acetylgalactosamine fragments. RNAi and ASO treatments induce an 80% decrease in TTR liver production for a period of 1 to 12 weeks. ASO and RNAi phase 3 trials in patients with TTR-related polyneuropathy have shown a positive impact on neuropathy clinical scores and quality of life end points, and delayed RNAi treatment negatively affects survival. Clinical trials specifically investigating RNAi therapy in TTR cardiomyopathy are underway. Hepatic RNA targeting has revolutionized ATTRv treatment and may allow for the transforming a fatal disease into a treatable disorder. Because retina and choroid plexus secrete limited quantities of TTR protein, both tissues are now seen as the next targets for fully controlling the disease.
Topics: Adult; Humans; Oligonucleotides, Antisense; RNA Interference; Quality of Life; CRISPR-Cas Systems; Amyloid Neuropathies, Familial; Oligonucleotides; RNA
PubMed: 37624911
DOI: 10.1182/blood.2023019884 -
Biosensors Apr 2024The rapid and sensitive detection of pathogenic bacteria is becoming increasingly important for the timely prevention of contamination and the treatment of infections.... (Review)
Review
The rapid and sensitive detection of pathogenic bacteria is becoming increasingly important for the timely prevention of contamination and the treatment of infections. Biosensors based on nucleic acid aptamers, integrated with optical, electrochemical, and mass-sensitive analytical techniques, have garnered intense interest because of their versatility, cost-efficiency, and ability to exhibit high affinity and specificity in binding bacterial biomarkers, toxins, and whole cells. This review highlights the development of aptamers, their structural characterization, and the chemical modifications enabling optimized recognition properties and enhanced stability in complex biological matrices. Furthermore, recent examples of aptasensors for the detection of bacterial cells, biomarkers, and toxins are discussed. Finally, we explore the barriers to and discuss perspectives on the application of aptamer-based bacterial detection.
Topics: Biosensing Techniques; Aptamers, Nucleotide; Bacteria; Humans; Electrochemical Techniques; Biomarkers
PubMed: 38785684
DOI: 10.3390/bios14050210 -
International Journal of Molecular... Jul 2023Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell...
Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin-1β (IL-1β) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL-1β induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.
Topics: Animals; Humans; Male; NF-kappa B; Matrix Metalloproteinase 13; Polynucleotides; Cells, Cultured; Semen; Inflammation; Osteoarthritis; Chondrocytes; Anti-Inflammatory Agents; Hypertrophy; Interleukin-1beta
PubMed: 37569659
DOI: 10.3390/ijms241512282 -
European Biophysics Journal : EBJ Oct 2023Peptide nucleic acid (PNA) is a nucleic acid mimic with high specificity and binding affinity to natural DNA or RNA, as well as resistance to enzymatic degradation. PNA... (Review)
Review
Peptide nucleic acid (PNA) is a nucleic acid mimic with high specificity and binding affinity to natural DNA or RNA, as well as resistance to enzymatic degradation. PNA sequences can be designed to selectively silence gene expression, which makes PNA a promising tool for antimicrobial applications. However, the poor membrane permeability of PNA remains the main limiting factor for its applications in cells. To overcome this obstacle, PNA conjugates with different molecules have been developed. This mini-review focuses on covalently linked conjugates of PNA with cell-penetrating peptides, aminosugars, aminoglycoside antibiotics, and non-peptidic molecules that were tested, primarily as PNA carriers, in antibacterial and antiviral applications. The chemistries of the conjugation and the applied linkers are also discussed.
Topics: Peptide Nucleic Acids; Anti-Bacterial Agents; Amino Acid Sequence; Cell-Penetrating Peptides
PubMed: 37610696
DOI: 10.1007/s00249-023-01673-w -
Analytical Methods : Advancing Methods... Nov 2023Heavy metal ion contamination poses significant environmental and health risks, necessitating rapid and efficient detection methods. In the last decade, colorimetric... (Review)
Review
Heavy metal ion contamination poses significant environmental and health risks, necessitating rapid and efficient detection methods. In the last decade, colorimetric aptasensors have emerged as powerful tools for heavy metal ion detection, owing to their notable attributes such as high specificity, facile synthesis, adaptability to modifications, long-term stability, and heightened sensitivity. This comprehensive overview summarizes the key developments in this field over the past ten years. It discusses the principles, design strategies, and innovative techniques employed in colorimetric aptasensors using nanomaterials. Recent advancements in enhancing sensitivity, selectivity, and on-site applicability are highlighted. The review also presents application studies of successful heavy metal ion detection using colorimetric aptasensors, underlining their potential for environmental monitoring and health protection. Finally, future directions and challenges in the continued evolution of these aptasensors are outlined.
Topics: Colorimetry; Biosensing Techniques; Aptamers, Nucleotide; Metals, Heavy; Nanostructures
PubMed: 37965993
DOI: 10.1039/d3ay01815f -
Advanced Healthcare Materials Dec 2023Pharmacological strategies to activate innate immune cells are of great relevance in the context of vaccine design and anticancer immune therapy, to mount broad immune...
Pharmacological strategies to activate innate immune cells are of great relevance in the context of vaccine design and anticancer immune therapy, to mount broad immune responses able to clear infection and malignant cells. Synthetic CpG oligodeoxynucleotides (CpG-ODNs) are short single-stranded DNA molecules containing unmethylated CpG dinucleotides and a phosphorothioate backbone. Class B CpG ODNs activate robust innate immune responses through a TLR9-dependent NF-κB signaling pathway. This feature is attractive to exploit in the context of vaccine design and cancer immunotherapy. Soluble CpG-ODNs cause hepatic toxicity, which reduces its therapeutic applicability. The formulation of class B CpG ODN1826 in lipid nanoparticles (LNPs) containing an ionizable cationic lipid that complexes CpG through electrostatic interaction is reported. Upon local administration, LNP-formulated CpG drains to lymph nodes and triggers robust innate immune activation. Unformulated, soluble, CpG, by contrast, is unable to induce robust innate activation in draining lymph nodes and is distributed systemically. In a vaccination setting, LNP-formulated CpG, admixed with a protein antigen, induces higher antigen-specific antibody titers and T cell responses than antigen admixed with unformulated soluble CpG.
Topics: Toll-Like Receptor 9; Adjuvants, Immunologic; Immunity, Innate; Lymphoid Tissue; Vaccines; Oligodeoxyribonucleotides
PubMed: 37772637
DOI: 10.1002/adhm.202301687 -
Biomacromolecules Nov 2023The continuous evolution and spread of common pathogenic bacteria is a major challenge in diagnosis and treatment with current biotechnology and modern molecular... (Review)
Review
The continuous evolution and spread of common pathogenic bacteria is a major challenge in diagnosis and treatment with current biotechnology and modern molecular medicine. To confront this challenge, scientists urgently need to find alternatives for traditional antimicrobial agents. Various bacteriostatic aptamers obtained through SELEX screening are one of the most promising strategies. These bacteriostatic aptamers can reduce bacterial infection by blocking bacterial toxin infiltration, inhibiting biofilm formation, preventing bacterial invasion of immune cells, interfering with essential biochemical processes, and other mechanisms. In addition, aptamers may also help enhance the function of other antibacterial materials/drugs when used in combination. This paper has reviewed the bacteriostatic aptamers in the treatment of common pathogenic bacteria infections. For this aspect, first, bacteriostatic aptamers and their screening strategies are summarized. Then, the effect of molecular tailoring and modification on the performance of the bacteriostatic aptamer is analyzed, and the antibacterial mechanism and antibacterial strategy based on aptamers are introduced. Finally, the key technical challenges and their development prospects in clinical treatment are also carefully discussed.
Topics: Humans; Aptamers, Nucleotide; Bacterial Infections; Bacteria; Anti-Bacterial Agents; SELEX Aptamer Technique
PubMed: 37728999
DOI: 10.1021/acs.biomac.3c00634 -
Angewandte Chemie (International Ed. in... Nov 2023DNA nanotechnology provides an approach to create precise, tunable, and biocompatible nanostructures for biomedical applications. However, the stability of these...
DNA nanotechnology provides an approach to create precise, tunable, and biocompatible nanostructures for biomedical applications. However, the stability of these structures is severely compromised in biological milieu due to their fast degradation by nucleases. Recently, we showed how enzymatic polymerization could be harnessed to grow polynucleotide brushes of tunable length and location on the surface of DNA origami nanostructures, which greatly enhances their nuclease stability. Here, we report on strategies that allow for both spatial and temporal control over polymerization through activatable initiation, cleavage, and regeneration of polynucleotide brushes using restriction enzymes. The ability to site-specifically decorate DNA origami nanostructures with polynucleotide brushes in a spatiotemporally controlled way provides access to "smart" functionalized DNA architectures with potential applications in drug delivery and supramolecular assembly.
Topics: Polynucleotides; Nanostructures; DNA; Nanotechnology; Drug Delivery Systems; Nucleic Acid Conformation
PubMed: 37820028
DOI: 10.1002/anie.202311727 -
Mikrochimica Acta Aug 2023The measurement of food contaminants faces a great challenge owing to the increasing demand for safe food, increasing consumption of fast food, and rapidly changing... (Review)
Review
The measurement of food contaminants faces a great challenge owing to the increasing demand for safe food, increasing consumption of fast food, and rapidly changing patterns of human consumption. As different types of contaminants in food products can pose different levels of threat to human health, it is desirable to develop specific and rapid methods for their identification and quantification. During the past few years, metal-organic framework (MOF)-based materials have been extensively explored in the development of food safety sensors. MOFs are porous crystalline materials with tunable composition, dynamic porosity, and facile surface functionalization. The construction of high-performance biosensors for a range of applications (e.g., food safety, environmental monitoring, and biochemical diagnostics) can thus be promoted through the synergistic combination of MOFs with aptamers. Accordingly, this review article delineates recent innovations achieved for the aptamer-functionalized MOFs toward the detection of food contaminants. First, we describe the basic concepts involved in the detection of food contaminants in terms of the advantages and disadvantages of the commonly used analytical methods (e.g., DNA-based methods (PCR/real-time PCR/multiplex PCR/digital PCR) and protein-based methods (enzyme-linked immunosorbent assay/immunochromatography assay/immunosensor/mass spectrometry). Afterward, the progress in aptamer-functionalized MOF biosensors is discussed with respect to the sensing mechanisms (e.g., the role of MOFs as signal probes and carriers for loading signal probes) along with their performance evaluation (e.g., in terms of sensitivity). We finally discuss challenges and opportunities associated with the development of aptamer-functionalized MOFs for the measurement of food contaminants.
Topics: Humans; Metal-Organic Frameworks; Biosensing Techniques; Immunoassay; Oligonucleotides; Food, Processed
PubMed: 37646854
DOI: 10.1007/s00604-023-05937-2