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Diagnostic Aptamers in Present and Future Tense

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 45883

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Special Issue Editor

Dr. Tamás Mészáros

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Guest Editor

Department of Molecular Biology, Institute of of Biochemistry and Molecular Biology, Semmelweis University, H-1094 Budapest, Hungary
Interests: functional analysis of proteins by in vitro translation; aptamer generation for diagnostic purposes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Although the significance of image analysis continuously increases, highly selective and quantitative detection of small molecules, nucleic acid and protein biomarkers, and infectious organisms remains to be the mainstay of diagnostics. The selectivity of this latter diagnostic approach is typically ensured by leveraging the discriminating capacity of antibodies. In the last decade, literally thousands of papers have attested that the selectivity and affinity of aptamers are comparable or even superior to those of antibodies. Furthermore, due to their straightforward production and ideal chemical properties, aptamers could be the method of choice for the development of diagnostic devices. In spite of their advantageous characteristics and panel of proof-of-principle studies demonstrating their sensor capability, aptamers have barely taken position in the routine diagnostics. This Special Edition aims at providing insight into the present status and the prospects of aptamers in medical, environmental, and food analysis. Some of the papers discuss the pitfalls of selection of aptamers for diagnostic purposes and the issues to be considered for increasing the success rate of generation of practically applicable aptamers. Another set of papers highlights the unique challenges of the development of aptamer-based analytical devices describing that this task is not equal to simply replacing antibodies with aptamers. Finally, we show examples of commercialized kits and systems that could indicate a prosperous future for aptamers in diagnostics.

Dr. Tamás Mészáros
Guest Editor

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Keywords

small molecule
biomarker protein
virus selective aptamers
rationally designed selection
aptamers as a sensor of diagnostic systems

Published Papers (11 papers)

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Research

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11 pages, 1361 KiB

Open AccessArticle

Spiegelmer-Based Sandwich Assay for Cardiac Troponin I Detection

by Zoltán János Tolnai, Judit András, Zsuzsanna Szeitner, Krisztina Percze, László Ferenc Simon, Róbert E. Gyurcsányi and Tamás Mészáros

Int. J. Mol. Sci. 2020, 21(14), 4963; https://doi.org/10.3390/ijms21144963 - 14 Jul 2020

Cited by 7 | Viewed by 3401

Abstract

Two subunits of the ternary troponin complex, I and C, have cardiac muscle specific isoforms, and hence could be applied as highly-selective markers of acute coronary syndrome. We aimed at paving the way for the development of a robust cardiac troponin I-detecting sandwich assay by replacing antibodies with nuclease resistant aptamer analogues, so-called spiegelmers. To complement the previously generated spiegelmers that were specific for the N-terminus of cTnI, spiegelmers were selected for an amino acid stretch in the proximity of the C-terminal part of the protein by using a D-amino acid composed peptide. Following the selection, the oligonucleotides were screened by filter binding assay, and surface plasmon resonance analysis of the most auspicious candidates demonstrated that this approach could provide spiegelmers with subnanomolar dissociation constant. To demonstrate if the selected spiegelmers are functional and suitable for cTnI detection in a sandwich type arrangement, AlphaLisa technology was leveraged and the obtained results demonstrated that spiegelmers with different epitope selectivity are suitable for specific detection of cTnI protein even in human plasma containing samples. These results suggest that spiegelmers could be considered in the development of the next generation cTnI monitoring assays. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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18 pages, 4345 KiB

Open AccessArticle

Aptamer Cocktail to Detect Multiple Species of Mycoplasma in Cell Culture

by Quanyuan Wan, Xiaohui Liu, Zihua Zeng, Zhenghu Chen, Yanting Liu and Youli Zu

Int. J. Mol. Sci. 2020, 21(11), 3784; https://doi.org/10.3390/ijms21113784 - 27 May 2020

Cited by 9 | Viewed by 3653

Abstract

Mycoplasma contamination of cell line cultures is a common, yet often undetected problem in research laboratories. Many of the existing techniques to detect mycoplasma contamination of cultured cells are time-consuming, expensive, and have significant drawbacks. Here, we describe a mycoplasma detection system that is useful for detecting multiple species of mycoplasma in infected cell lines. The system contains three dye-labeled detection aptamers that can specifically bind to mycoplasma-infected cells and a dye-labeled control aptamer that minimally binds to cells. With this system, mycoplasma-contaminated cells can be detected within 30 min by using a flow cytometer, fluorescence microscope, or microplate reader. Further, this system may be used to detect mycoplasma-contaminated culture medium. This study presents an novel mycoplasma detection model that is simple, rapid, inexpensive, and sensitive. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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16 pages, 19449 KiB

Open AccessArticle

Modified DNA Aptamers for C-Reactive Protein and Lactate Dehydrogenase-5 with Sub-Nanomolar Affinities

by Hirotaka Minagawa, Yuka Kataoka, Hiroto Fujita, Masayasu Kuwahara, Katsunori Horii, Ikuo Shiratori and Iwao Waga

Int. J. Mol. Sci. 2020, 21(8), 2683; https://doi.org/10.3390/ijms21082683 - 13 Apr 2020

Cited by 11 | Viewed by 3422

Abstract

Human C-reactive protein (CRP) and lactate dehydrogenase are important markers in clinical laboratory testing—the former is used to detect in vivo inflammation, and the latter is used to detect cell necrosis and tissue destruction. We developed aptamers that bind to human CRP and human lactate dehydrogenase-5 (LDH-5) with high affinities (dissociation constants of 6.2 pM and 235 pM, respectively), applying the systematic evolution of ligands by exponential enrichment (SELEX) method, and by using a modified DNA library containing the following base-appended base modifications: analog adenine derivative at the fifth position of uracil (U^ad), analog guanine derivative at the fifth position of uracil (U^gu), and analog adenine derivative at the seventh position of adenine (A^ad). A potential application of these aptamers as sensor elements includes high-sensitivity target detection in point-of-care testing. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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Review

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18 pages, 542 KiB

Open AccessReview

Application of Aptamer-Based Assays to the Diagnosis of Arboviruses Important for Public Health in Brazil

by Ana Paula Corrêa Argondizzo, Dilson Silva and Sotiris Missailidis

Int. J. Mol. Sci. 2021, 22(1), 159; https://doi.org/10.3390/ijms22010159 - 26 Dec 2020

Cited by 3 | Viewed by 2394

Abstract

Arbovirus infections represent a global public health problem, and recent epidemics of yellow fever, dengue, and Zika have shown their critical importance in Brazil and worldwide. Whilst a major effort for vaccination programs has been in the spotlight, a number of aptamer approaches have been proposed in a complementary manner, offering the possibility of differential diagnosis between these arboviruses, which often present similar clinical symptoms, as well as the potential for a treatment option when no other alternative is available. In this review, we aim to provide a background on arbovirus, with a basic description of the main viral classes and the disease they cause, using the Brazilian context to build a comprehensive understanding of their role on a global scale. Subsequently, we offer an exhaustive revision of the diagnostic and therapeutic approaches offered by aptamers against arboviruses. We demonstrate how these promising reagents could help in the clinical diagnosis of this group of viruses, their use in a range of diagnostic formats, from biosensors to serological testing, and we give a short review on the potential approaches for novel aptamer-based antiviral treatment options against different arboviral diseases. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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19 pages, 1044 KiB

Open AccessReview

Novel Detection of Nasty Bugs, Prevention Is Better than Cure

by Mia Strom, Tamsyn Crowley and Sarah Shigdar

Int. J. Mol. Sci. 2021, 22(1), 149; https://doi.org/10.3390/ijms22010149 - 25 Dec 2020

Cited by 8 | Viewed by 2755

Abstract

Hospital-acquired infections (HAIs) are a growing concern around the world. They contribute to increasing mortality and morbidity rates and are an economic threat. All hospital patients have the potential to contract an HAI, but those with weakened or inferior immune systems are at highest risk. Most hospital patients will contract at least one HAI, but many will contract multiple ones. Bacteria are the most common cause of HAIs and contribute to 80–90% of all HAIs, with Staphylococcus aureus, Clostridium difficile, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae accounting for the majority. Each of these bacteria are highly resistant to antibiotics and can produce a protective film, known as a biofilm, to further prevent their eradication. It has been shown that by detecting and eradicating bacteria in the environment, infection rates can be reduced. The current methods for detecting bacteria are time consuming, non-specific, and prone to false negatives or false positives. Aptamer-based biosensors have demonstrated specific, time-efficient and simple detection, highlighting the likelihood that they could be used in a similar way to detect HAI-causing bacteria. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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40 pages, 4935 KiB

Open AccessReview

Aptamers against Immunoglobulins: Design, Selection and Bioanalytical Applications

by Zsófia Bognár and Róbert E. Gyurcsányi

Int. J. Mol. Sci. 2020, 21(16), 5748; https://doi.org/10.3390/ijms21165748 - 11 Aug 2020

Cited by 24 | Viewed by 4416

Abstract

Nucleic acid aptamers show clear promise as diagnostic reagents, as highly specific strands were reported against a large variety of biomarkers. They have appealing benefits in terms of reproducible generation by chemical synthesis, controlled modification with labels and functionalities providing versatile means for detection and oriented immobilization, as along with high biochemical and temperature resistance. Aptamers against immunoglobulin targets—IgA, IgM, IgG and IgE—have a clear niche for diagnostic applications, therefore numerous aptamers have been selected and used in combination with a variety of detection techniques. The aim of this review is to overview and evaluate aptamers selected for the recognition of antibodies, in terms of their design, analytical properties and diagnostic applications. Aptamer candidates showed convincing performance among others to identify stress and upper respiratory tract infection through SIgA detection, for cancer cell recognition using membrane bound IgM, to detect and treat hemolytic transfusion reactions, autoimmune diseases with IgG and detection of IgE for allergy diseases. However, in general, their use still lags significantly behind what their claimed benefits and the plethora of application opportunities would forecast. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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25 pages, 2558 KiB

Open AccessReview

Recent Progress in the Identification of Aptamers Against Bacterial Origins and Their Diagnostic Applications

by Nevina E. Trunzo and Ka Lok Hong

Int. J. Mol. Sci. 2020, 21(14), 5074; https://doi.org/10.3390/ijms21145074 - 18 Jul 2020

Cited by 21 | Viewed by 3798

Abstract

Aptamers have gained an increasing role as the molecular recognition element (MRE) in diagnostic assay development, since their first conception thirty years ago. The process to screen for nucleic acid-based binding elements (aptamers) was first described in 1990 by the Gold Laboratory. In the last three decades, many aptamers have been identified for a wide array of targets. In particular, the number of reports on investigating single-stranded DNA (ssDNA) aptamer applications in biosensing and diagnostic platforms have increased significantly in recent years. This review article summarizes the recent (2015 to 2020) progress of ssDNA aptamer research on bacteria, proteins, and lipids of bacterial origins that have implications for human infections. The basic process of aptamer selection, the principles of aptamer-based biosensors, and future perspectives will also be discussed. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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Graphical abstract

31 pages, 8779 KiB

Open AccessReview

Chemical Modification of Aptamers for Increased Binding Affinity in Diagnostic Applications: Current Status and Future Prospects

by Jan P. Elskens, Joke M. Elskens and Annemieke Madder

Int. J. Mol. Sci. 2020, 21(12), 4522; https://doi.org/10.3390/ijms21124522 - 25 Jun 2020

Cited by 85 | Viewed by 8978

Abstract

Aptamers are short single stranded DNA or RNA oligonucleotides that can recognize analytes with extraordinary target selectivity and affinity. Despite their promising properties and diagnostic potential, the number of commercial applications remains scarce. In order to endow them with novel recognition motifs and enhanced properties, chemical modification of aptamers has been pursued. This review focuses on chemical modifications, aimed at increasing the binding affinity for the aptamer’s target either in a non-covalent or covalent fashion, hereby improving their application potential in a diagnostic context. An overview of current methodologies will be given, thereby distinguishing between pre- and post-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) modifications. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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26 pages, 1218 KiB

Open AccessReview

Diagnostic and Therapeutic Value of Aptamers in Envenomation Cases

by Steven Ascoët and Michel De Waard

Int. J. Mol. Sci. 2020, 21(10), 3565; https://doi.org/10.3390/ijms21103565 - 18 May 2020

Cited by 12 | Viewed by 3056

Abstract

It is now more than a century since Albert Calmette from the Institut Pasteur changed the world of envenomation by demonstrating that antibodies raised against animal venoms have the ability to treat human victims of previously fatal bites or stings. Moreover, the research initiated at that time effectively launched the discipline of toxicology, first leading to the search for toxic venom components, followed by the demonstration of venoms that also contained compounds of therapeutic value. Interest from pharmaceutical companies to treat envenomation is, however, declining, mainly for economic reasons, and hence, the World Health Organization has reclassified this public health issue to be a highest priority concern. While the production, storage, and safety of antivenom sera suffer from major inconveniences, alternative chemical and technological approaches to the problem of envenomation need to be considered that bypass the use of antibodies for toxin neutralization. Herein, we review an emerging strategy that relies on the use of aptamers and discuss how close—or otherwise—we are to finding a viable alternative to the use of antibodies for the therapy of human envenomation. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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15 pages, 1458 KiB

Open AccessReview

SERS-Based Biosensors for Virus Determination with Oligonucleotides as Recognition Elements

by Oganes Ambartsumyan, Dmitry Gribanyov, Vladimir Kukushkin, Alexey Kopylov and Elena Zavyalova

Int. J. Mol. Sci. 2020, 21(9), 3373; https://doi.org/10.3390/ijms21093373 - 10 May 2020

Cited by 50 | Viewed by 5033

Abstract

Viral infections are among the main causes of morbidity and mortality of humans; sensitive and specific diagnostic methods for the rapid identification of viral pathogens are required. Surface-enhanced Raman spectroscopy (SERS) is one of the most promising techniques for routine analysis due to its excellent sensitivity, simple and low-cost instrumentation and minimal required sample preparation. The outstanding sensitivity of SERS is achieved due to tiny nanostructures which must be assembled before or during the analysis. As for specificity, it may be provided using recognition elements. Antibodies, complimentary nucleic acids and aptamers are the most usable recognition elements for virus identification. Here, SERS-based biosensors for virus identification with oligonucleotides as recognition elements are reviewed, and the potential of these biosensors is discussed. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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Graphical abstract

23 pages, 774 KiB

Open AccessReview

Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases

by Valentina Giudice, Francesca Mensitieri, Viviana Izzo, Amelia Filippelli and Carmine Selleri

Int. J. Mol. Sci. 2020, 21(9), 3252; https://doi.org/10.3390/ijms21093252 - 04 May 2020

Cited by 23 | Viewed by 4424

Abstract

Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability, and resistance to nuclease degradation. Aptamers and SOMAmers are largely employed for multiplex high-throughput proteomics analysis with high reproducibility and reliability, for tumor cell detection by flow cytometry or microscopy for research and clinical purposes. In addition, aptamers are increasingly used for novel drug delivery systems specifically targeting tumor cells, and as new anticancer molecules. In this review, we summarize current preclinical and clinical applications of aptamers in malignant and non-malignant hematological diseases. Full article

(This article belongs to the Special Issue Diagnostic Aptamers in Present and Future Tense)

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