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Theranostics 2023A diverse array of organic and inorganic materials, including nanomaterials, has been extensively employed in multifunctional biomedical applications. These applications... (Review)
Review
A diverse array of organic and inorganic materials, including nanomaterials, has been extensively employed in multifunctional biomedical applications. These applications encompass drug/gene delivery, tissue engineering, biosensors, photodynamic and photothermal therapy, and combinatorial sciences. Surface and bulk engineering of these materials, by incorporating biomolecules and aptamers, offers several advantages such as decreased cytotoxicity, improved stability, enhanced selectivity/sensitivity toward specific targets, and expanded multifunctional capabilities. In this comprehensive review, we specifically focus on aptamer-modified engineered materials for diverse biomedical applications. We delve into their mechanisms, advantages, and challenges, and provide an in-depth analysis of relevant literature references. This critical evaluation aims to enhance the scientific community's understanding of this field and inspire new ideas for future research endeavors.
Topics: Precision Medicine; Drug Delivery Systems; Nanostructures; Aptamers, Nucleotide; Biosensing Techniques
PubMed: 37908725
DOI: 10.7150/thno.85419 -
Chemical Reviews Nov 2023Serving as the basis of cell life, interactions between nucleic acids and proteins play essential roles in fundamental cellular processes. Aptamers are unique... (Review)
Review
Serving as the basis of cell life, interactions between nucleic acids and proteins play essential roles in fundamental cellular processes. Aptamers are unique single-stranded oligonucleotides generated by in vitro evolution methods, possessing the ability to interact with proteins specifically. Altering the structure of aptamers will largely modulate their interactions with proteins and further affect related cellular behaviors. Recently, with the in-depth research of aptamer-protein interactions, the analytical assays based on their interactions have been widely developed and become a powerful tool for biomolecular detection. There are some insightful reviews on aptamers applied in protein detection, while few systematic discussions are from the perspective of regulating aptamer-protein interactions. Herein, we comprehensively introduce the methods for regulating aptamer-protein interactions and elaborate on the detection techniques for analyzing aptamer-protein interactions. Additionally, this review provides a broad summary of analytical assays based on the regulation of aptamer-protein interactions for detecting biomolecules. Finally, we present our perspectives regarding the opportunities and challenges of analytical assays for biological analysis, aiming to provide guidance for disease mechanism research and drug discovery.
Topics: Aptamers, Nucleotide; Proteins; Nucleic Acids; SELEX Aptamer Technique
PubMed: 37931070
DOI: 10.1021/acs.chemrev.3c00377 -
Biomacromolecules Aug 2023Rapid and specific assaying of molecules that report on a pathophysiological condition, environmental pollution, or drug concentration is pivotal for establishing... (Review)
Review
Rapid and specific assaying of molecules that report on a pathophysiological condition, environmental pollution, or drug concentration is pivotal for establishing efficient and accurate diagnostic systems. One of the main components required for the construction of these systems is the recognition element (receptor) that can identify target analytes. Oligonucleotide switching structures, or aptamers, have been widely studied as selective receptors that can precisely identify targets in different analyzed matrices with minimal interference from other components in an antibody-like recognition process. These aptasensors, especially when integrated into sensing platforms, enable a multitude of sensors that can outperform antibody-based sensors in terms of flexibility of the sensing strategy and ease of deployment to areas with limited resources. Research into compounds that efficiently enhance signal transduction and provide a suitable platform for conjugating aptamers has gained huge momentum over the past decade. The multifaceted nature of conjugated polymers (CPs), notably their versatile electrical and optical properties, endows them with a broad range of potential applications in optical, electrical, and electrochemical signal transduction. Despite the substantial body of research demonstrating the enhanced performance of sensing devices using doped or nanostructure-embedded CPs, few reviews are available that specifically describe the use of conjugated polymers in aptasensing. The purpose of this review is to bridge this gap and provide a comprehensive description of a variety of CPs, from a historical viewpoint, underpinning their specific characteristics and demonstrating the advances in biosensors associated with the use of these conjugated polymers.
Topics: Polymers; Biosensing Techniques; Antibodies; Oligonucleotides; Electricity
PubMed: 37462615
DOI: 10.1021/acs.biomac.3c00050 -
Cell Mar 2024Mapping the intricate spatial relationships between the many different molecules inside a cell is essential to understanding cellular functions in all their complexity....
Mapping the intricate spatial relationships between the many different molecules inside a cell is essential to understanding cellular functions in all their complexity. Super-resolution fluorescence microscopy offers the required spatial resolution but struggles to reveal more than four different targets simultaneously. Exchanging labels in subsequent imaging rounds for multiplexed imaging extends this number but is limited by its low throughput. Here, we present a method for rapid multiplexed super-resolution microscopy that can, in principle, be applied to a nearly unlimited number of molecular targets by leveraging fluorogenic labeling in conjunction with transient adapter-mediated switching for high-throughput DNA-PAINT (FLASH-PAINT). We demonstrate the versatility of FLASH-PAINT with four applications: mapping nine proteins in a single mammalian cell, elucidating the functional organization of primary cilia by nine-target imaging, revealing the changes in proximity of thirteen different targets in unperturbed and dissociated Golgi stacks, and investigating and quantifying inter-organelle contacts at 3D super-resolution.
Topics: Animals; DNA; Golgi Apparatus; Mammals; Microscopy, Fluorescence; Oligonucleotides; Proteins
PubMed: 38552613
DOI: 10.1016/j.cell.2024.02.033 -
Chembiochem : a European Journal of... Sep 2023Signal transduction from non-nucleic acid ligands (small molecules and proteins) to structural changes of nucleic acids plays a crucial role in both biomedical analysis... (Review)
Review
Signal transduction from non-nucleic acid ligands (small molecules and proteins) to structural changes of nucleic acids plays a crucial role in both biomedical analysis and cellular regulations. However, how to bridge between these two types of molecules without compromising the expandable complexity and programmability of the nucleic acid nanomachines is a critical challenge. Compared with the previously most widely applied transduction strategies, we review the latest advances of a kinetically controlled approach for ligand-oligonucleotide transduction in this Concept article. This new design works through an intrinsic conformational alteration of the nucleic acid aptamer upon the ligand binding as a governing factor for nucleic acid strand displacement reactions. The functionalities and applications of this transduction system as a ligand converter on biosensing and DNA computation are described and discussed. Furthermore, we propose some potential scenarios for utilization of this ligand transduction design to regulate gene expression through synthetic RNA switches in the cellular contexts. Finally, future perspectives regarding this ligand-oligonucleotide transduction platform are also discussed.
Topics: Nucleic Acids; Ligands; Proteins; Oligonucleotides; Biosensing Techniques
PubMed: 37401635
DOI: 10.1002/cbic.202300292 -
International Journal of Nanomedicine 2023Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye... (Review)
Review
Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye disorders has not been well-documented. The current literature on aptamers was reviewed in this study. Aptamer-related drugs and biochemical sensors have been evaluated for several eye disorders within the past decade; S58 targeting TGF-β receptor II and pegaptanib targeting vascular endothelial growth factor (VEGF) are used to prevent fibrosis after glaucoma filtration surgery. Anti-brain-derived neurotrophic factor aptamer has been used to diagnose glaucoma. The first approved aptamer drug (pegaptanib) has been used to inhibit angiogenesis in age-related macular degeneration (AMD) and diabetic retinopathy (DR), and its efficacy and safety have been demonstrated in clinical trials. Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers, such as C promoter binding factor 1, CD44, and advanced end products in AMD and DR, targeting other signal pathway proteins have also been discovered for therapy, and biochemical sensors for early diagnosis have been developed based on aptamers targeting VEGF, connective tissue growth factor, and lipocalin 1. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.
Topics: Humans; Vascular Endothelial Growth Factor A; Ophthalmology; Macular Degeneration; Aptamers, Nucleotide; Diabetic Retinopathy; Glaucoma; Acceleration
PubMed: 37551274
DOI: 10.2147/IJN.S418115 -
Nanoscale Sep 2023Nanozymes are inorganic, organic and metal-organic framework nanoparticles that reveal catalytic functions by emulating native enzyme activities. Recently, these... (Review)
Review
Nanozymes are inorganic, organic and metal-organic framework nanoparticles that reveal catalytic functions by emulating native enzyme activities. Recently, these nanozymes have attracted growing scientific interest, finding diverse analytical and medical applications. However, the catalytic activities and functions of nanozymes are limited, due to the lack of substrate binding sites that concentrate on the substrate at the catalytic site (molarity effect), introduce substrate specificity and allow functional complexity of the catalysts (cascaded, switchable and cooperative catalysis). The modification of nanozymes with functional nucleic acids provides means to overcome these limitations and engineer nucleic acid/nanozyme hybrids for diverse applications. This is exemplified with the synthesis of aptananozymes, which are supramolecular aptamer-modified nanozymes. Aptananozymes exhibit combined specific binding and catalytic properties that drive diverse chemical transformations, revealing enhanced catalytic activities, as compared to the separated nanozyme/aptamer constituents. Relationships of structure-catalytic functions in the aptananozyme constructs are demonstrated. In addition, modification of nanozymes exhibiting multimodal catalytic functions with aptamers allows the engineering of nanozyme-based bioreactors for cascaded catalysis. Also, the functionalization of reactive oxygen species (ROS)-generating nanozymes with cancer cell-recognizing aptamers yields aptananozymes for targeted chemodynamic treatment of cancer cells and cancer tumors elicited in mice. Finally, nucleic acid-modified enzyme (glucose oxidase)-loaded metal-organic framework nanoparticles yield switchable biocatalytic nanozymes that drive the ON/OFF biocatalyzed oxidation of Amplex Red, dopamine or the generation of chemiluminescence. Herein, future challenges of the topic are addressed.
Topics: Animals; Mice; Metal-Organic Frameworks; Binding Sites; Biocatalysis; Catalysis; Nucleic Acids; Oligonucleotides
PubMed: 37646290
DOI: 10.1039/d3nr02345a -
Journal of Molecular Biology Dec 2023Poly(UG) or "pUG" RNAs are UG or GU dinucleotide repeat sequences which are highly abundant in eukaryotes. Post-transcriptional addition of pUGs to RNA 3' ends marks...
Poly(UG) or "pUG" RNAs are UG or GU dinucleotide repeat sequences which are highly abundant in eukaryotes. Post-transcriptional addition of pUGs to RNA 3' ends marks mRNAs as vectors for gene silencing in C. elegans. We previously determined the crystal structure of pUG RNA bound to the ligand N-methyl mesoporphyrin IX (NMM), but the structure of free pUG RNA is unknown. Here we report the solution structure of the free pUG RNA (GU), as determined by nuclear magnetic resonance spectroscopy and small and wide-angle x-ray scattering (NMR-SAXS-WAXS). The low complexity sequence and 4-fold symmetry of the structure result in overlapped NMR signals that complicate chemical shift assignment. We therefore utilized single site-specific deoxyribose modifications which did not perturb the structure and introduced well-resolved methylene signals that are easily identified in NMR spectra. The solution structure ensemble has a root mean squared deviation (RMSD) of 0.62 Å and is a compact, left-handed quadruplex with a Z-form backbone, or "pUG fold." Overall, the structure agrees with the crystal structure of (GU) bound to NMM, indicating the pUG fold is unaltered by docking of the NMM ligand. The solution structure reveals conformational details that could not be resolved by x-ray crystallography, which explain how the pUG fold can form within longer RNAs.
Topics: Animals; Caenorhabditis elegans; Crystallography, X-Ray; Ligands; Models, Molecular; RNA; Scattering, Small Angle; X-Ray Diffraction; Poly U; Poly G; Nucleic Acid Conformation
PubMed: 37924862
DOI: 10.1016/j.jmb.2023.168340 -
Drugs Jun 2024Increasing evidence has implicated lipoprotein(a) [Lp(a)] in the causality of atherosclerosis and calcific aortic stenosis. This has stimulated immense interest in... (Review)
Review
Increasing evidence has implicated lipoprotein(a) [Lp(a)] in the causality of atherosclerosis and calcific aortic stenosis. This has stimulated immense interest in developing novel approaches to integrating Lp(a) into the setting of cardiovascular prevention. Current guidelines advocate universal measurement of Lp(a) levels, with the potential to influence cardiovascular risk assessment and triage of higher-risk patients to use of more intensive preventive therapies. In parallel, considerable activity has been undertaken to develop novel therapeutics with the potential to achieve selective and substantial reductions in Lp(a) levels. Early studies of antisense oligonucleotides (e.g., mipomersen, pelacarsen), RNA interference (e.g., olpasiran, zerlasiran, lepodisiran) and small molecule inhibitors (e.g., muvalaplin) have demonstrated effective Lp(a) lowering and good tolerability. These agents are moving forward in clinical development, in order to determine whether Lp(a) lowering reduces cardiovascular risk. The results of these studies have the potential to transform our approach to the prevention of cardiovascular disease.
Topics: Humans; Lipoprotein(a); Cardiovascular Diseases; Oligonucleotides, Antisense; Atherosclerosis; RNA Interference; Oligonucleotides; Animals
PubMed: 38849700
DOI: 10.1007/s40265-024-02046-z -
Angewandte Chemie (International Ed. in... Feb 2024Photochromism is a reversible phenomenon wherein a material undergoes a change in color upon exposure to light. In organic photochromes, this effect often results from... (Review)
Review
Photochromism is a reversible phenomenon wherein a material undergoes a change in color upon exposure to light. In organic photochromes, this effect often results from light-induced isomerization reactions, leading to alterations in either the spatial orientation or electronic properties of the photochrome. The incorporation of photochromic moieties into biomolecules, such as proteins or nucleic acids, has become a prevalent approach to render these biomolecules responsive to light stimuli. Utilizing light as a trigger for the manipulation of biomolecular structure and function offers numerous advantages compared to other stimuli, such as chemical or electrical treatments, due to its non-invasive nature. Consequently, light proves particularly advantageous in cellular and tissue applications. In this review, we emphasize recent advancements in the field of photochromic nucleosides and oligonucleotides. We provide an overview of the design principles of different classes of photochromes, synthetic strategies, critical analytical challenges, as well as structure-property relationships. The applications of photochromic nucleic acid derivatives encompass diverse domains, ranging from the precise photoregulation of gene expression to the controlled modulation of the three-dimensional structures of oligonucleotides and the development of DNA-based fluorescence modulators. Moreover, we present a future perspective on potential modifications and applications.
Topics: Oligonucleotides; Nucleosides; DNA; Nucleic Acids
PubMed: 37966433
DOI: 10.1002/anie.202310797