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Aptamers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 October 2017) | Viewed by 115660

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Special Issue Editors

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China
Interests: directed molecular evolution; aptamers; diagnostics; sensing; bioinformatics; modelling of complex systems
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

Special Issue Information

Dear Colleagues,

Aptamers are oligonucleotides capable of specific, high affinity binding to a wide variety of target molecules. These attributes have led to their application in diagnostics, therapeutics, targeted delivery, fluorescence imaging, as well as biosensing. The methods by which aptamers are selected have been iteratively improved for almost three decades, yielding a robust system capable of producing aptamers rapidly and at low cost with many advantages relative to antibodies. In recent years, there has been an explosion of innovation in aptamer science including enhanced selection techniques, riboswitches, unnatural base pairs, nucleic acid nanostructures, DNAzymes and aptazymes. This Special Issue of IJMS will cover a selection of research topics and current review articles highlighting work at the frontiers of aptamer research and applications.

Dr. Julian Alexander Tanner
Dr. Andrew Kinghorn
Dr. Yee-Wai Cheung
Guest Editors

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Keywords

  • Aptamers
  • SELEX
  • Diagnostics
  • Therapeutics
  • Biosensing
  • Riboswitch
  • DNAzyme
  • Unnatural base pairs
  • XNA
  • Nucleic acid

Published Papers (15 papers)

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Research

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15 pages, 2421 KiB  
Article
Selection and Characterization of a DNA Aptamer Specifically Targeting Human HECT Ubiquitin Ligase WWP1
by Wesley O. Tucker, Andrew B. Kinghorn, Lewis A. Fraser, Yee-Wai Cheung and Julian A. Tanner
Int. J. Mol. Sci. 2018, 19(3), 763; https://doi.org/10.3390/ijms19030763 - 07 Mar 2018
Cited by 18 | Viewed by 5104
Abstract
Nucleic acid aptamers hold promise as therapeutic tools for specific, tailored inhibition of protein targets with several advantages when compared to small molecules or antibodies. Nuclear WW domain containing E3 ubiquitin ligase 1 (WWP1) ubiquitin ligase poly-ubiquitinates Runt-related transcription factor 2 (Runx2), a [...] Read more.
Nucleic acid aptamers hold promise as therapeutic tools for specific, tailored inhibition of protein targets with several advantages when compared to small molecules or antibodies. Nuclear WW domain containing E3 ubiquitin ligase 1 (WWP1) ubiquitin ligase poly-ubiquitinates Runt-related transcription factor 2 (Runx2), a key transcription factor associated with osteoblast differentiation. Since WWP1 and an adapter known as Schnurri-3 are negative regulators of osteoblast function, the disruption of this complex has the potential to increase bone deposition for osteoporosis therapy. Here, we develop new DNA aptamers that bind and inhibit WWP1 then investigate efficacy in an osteoblastic cell culture. DNA aptamers were selected against three different truncations of the HECT domain of WWP1. Aptamers which bind specifically to a C-lobe HECT domain truncation were observed to enrich during the selection procedure. One particular DNA aptamer termed C3A was further evaluated for its ability to bind WWP1 and inhibit its ubiquitination activity. C3A showed a low µM binding affinity to WWP1 and was observed to be a non-competitive inhibitor of WWP1 HECT ubiquitin ligase activity. When SaOS-2 osteoblastic cells were treated with C3A, partial localization to the nucleus was observed. The C3A aptamer was also demonstrated to specifically promote extracellular mineralization in cell culture experiments. The C3A aptamer has potential for further development as a novel osteoporosis therapeutic strategy. Our results demonstrate that aptamer-mediated inhibition of protein ubiquitination can be a novel therapeutic strategy. Full article
(This article belongs to the Special Issue Aptamers)
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9769 KiB  
Article
In Vitro Selection of a Single-Stranded DNA Molecular Recognition Element against the Pesticide Fipronil and Sensitive Detection in River Water
by Ka L. Hong and Letha J. Sooter
Int. J. Mol. Sci. 2018, 19(1), 85; https://doi.org/10.3390/ijms19010085 - 28 Dec 2017
Cited by 28 | Viewed by 5137
Abstract
Fipronil is a commonly used insecticide that has been shown to have environmental and human health risks. The current standard methods of detection for fipronil and its metabolites, such as GC-MS, are time consuming and labor intensive. In this study, a variant of [...] Read more.
Fipronil is a commonly used insecticide that has been shown to have environmental and human health risks. The current standard methods of detection for fipronil and its metabolites, such as GC-MS, are time consuming and labor intensive. In this study, a variant of systematic evolution of ligands by exponential enrichment (SELEX), was utilized to identify the first single-stranded DNA (ssDNA) molecular recognition element (MRE) that binds to fipronil with high affinity (Kd = 48 ± 8 nM). The selected MRE displayed low cross binding activity on various environmentally relevant, structurally unrelated herbicides and pesticides, in addition to broad-spectrum binding activity on major metabolites of fipronil and a structurally similar pesticide in prepared river samples. Additionally, a proof-of-principle fluorescent detection assay was developed by using the selected ssDNA MRE as a signal-reporting element, with a limit of detection of 105 nM in a prepared river water sample. Full article
(This article belongs to the Special Issue Aptamers)
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2767 KiB  
Article
Development of An Impedimetric Aptasensor for the Detection of Staphylococcus aureus
by Peggy Reich, Regina Stoltenburg, Beate Strehlitz, Dieter Frense and Dieter Beckmann
Int. J. Mol. Sci. 2017, 18(11), 2484; https://doi.org/10.3390/ijms18112484 - 21 Nov 2017
Cited by 57 | Viewed by 7318
Abstract
In combination with electrochemical impedance spectroscopy, aptamer-based biosensors are a powerful tool for fast analytical devices. Herein, we present an impedimetric aptasensor for the detection of the human pathogen Staphylococcus aureus. The used aptamer targets protein A, a surface bound virulence factor [...] Read more.
In combination with electrochemical impedance spectroscopy, aptamer-based biosensors are a powerful tool for fast analytical devices. Herein, we present an impedimetric aptasensor for the detection of the human pathogen Staphylococcus aureus. The used aptamer targets protein A, a surface bound virulence factor of S. aureus. The thiol-modified protein A-binding aptamer was co-immobilized with 6-mercapto-1-hexanol onto gold electrodes by self-assembly. Optimization of the ratio of aptamer to 6-mercapto-1-hexanol resulted in an average density of 1.01 ± 0.44 × 1013 aptamer molecules per cm2. As shown with quartz crystal microbalance experiments, the immobilized aptamer retained its functionality to bind recombinant protein A. Our impedimetric biosensor is based on the principle that binding of target molecules to the immobilized aptamer decreases the electron transfer between electrode and ferri-/ferrocyanide in solution, which is measured as an increase of impedance. Microscale thermophoresis measurements showed that addition of the redox probe ferri-/ferrocyanide has no influence on the binding of aptamer and its target. We demonstrated that upon incubation with various concentrations of S. aureus, the charge-transfer resistance increased proportionally. The developed biosensor showed a limit of detection of 10 CFU·mL−1 and results were available within 10 minutes. The biosensor is highly selective, distinguishing non-target bacteria such as Escherichia coli and Staphylococcus epidermidis. This work highlights the immense potential of impedimetric aptasensors for future biosensing applications. Full article
(This article belongs to the Special Issue Aptamers)
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4468 KiB  
Article
Selection, Characterization and Interaction Studies of a DNA Aptamer for the Detection of Bifidobacterium bifidum
by Lujun Hu, Linlin Wang, Wenwei Lu, Jianxin Zhao, Hao Zhang and Wei Chen
Int. J. Mol. Sci. 2017, 18(5), 883; https://doi.org/10.3390/ijms18050883 - 25 Apr 2017
Cited by 16 | Viewed by 4772
Abstract
A whole-bacterium-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure was adopted in this study for the selection of an ssDNA aptamer that binds to Bifidobacterium bifidum. After 12 rounds of selection targeted against B. bifidum, 30 sequences were obtained [...] Read more.
A whole-bacterium-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure was adopted in this study for the selection of an ssDNA aptamer that binds to Bifidobacterium bifidum. After 12 rounds of selection targeted against B. bifidum, 30 sequences were obtained and divided into seven families according to primary sequence homology and similarity of secondary structure. Four FAM (fluorescein amidite) labeled aptamer sequences from different families were selected for further characterization by flow cytometric analysis. The results reveal that the aptamer sequence CCFM641-5 demonstrated high-affinity and specificity for B. bifidum compared with the other sequences tested, and the estimated Kd value was 10.69 ± 0.89 nM. Additionally, sequence truncation experiments of the aptamer CCFM641-5 led to the conclusion that the 5′-primer and 3′-primer binding sites were essential for aptamer-target binding. In addition, the possible component of the target B. bifidum, bound by the aptamer CCFM641-5, was identified as a membrane protein by treatment with proteinase. Furthermore, to prove the potential application of the aptamer CCFM641-5, a colorimetric bioassay of the sandwich-type structure was used to detect B. bifidum. The assay had a linear range of 104 to 107 cfu/mL (R2 = 0.9834). Therefore, the colorimetric bioassay appears to be a promising method for the detection of B. bifidum based on the aptamer CCFM641-5. Full article
(This article belongs to the Special Issue Aptamers)
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Review

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20 pages, 460 KiB  
Review
Aptamers Selected for Recognizing Amyloid β-Protein—A Case for Cautious Optimism
by Farid Rahimi
Int. J. Mol. Sci. 2018, 19(3), 668; https://doi.org/10.3390/ijms19030668 - 27 Feb 2018
Cited by 14 | Viewed by 4821
Abstract
Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid β-protein (Aβ) has been limited so far. Aβ is an intrinsically disordered protein that exists in a dynamic conformational equilibrium, presenting time-dependent [...] Read more.
Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid β-protein (Aβ) has been limited so far. Aβ is an intrinsically disordered protein that exists in a dynamic conformational equilibrium, presenting time-dependent ensembles of short-lived, metastable structures and assemblies that have been generally difficult to isolate and characterize. Moreover, despite understanding of potential physiological roles of Aβ, this peptide has been linked to the pathogenesis of Alzheimer disease, and its pathogenic roles remain controversial. Accumulated scientific evidence thus far highlights undesirable or nonspecific interactions between selected aptamers and different Aβ assemblies likely due to the metastable nature of Aβ or inherent affinity of RNA oligonucleotides to β-sheet-rich fibrillar structures of amyloidogenic proteins. Accordingly, lessons drawn from Aβ–aptamer studies emphasize that purity and uniformity of the protein target and rigorous characterization of aptamers’ specificity are important for realizing and garnering the full potential of aptamers selected for recognizing Aβ or other intrinsically disordered proteins. This review summarizes studies of aptamers selected for recognizing different Aβ assemblies and highlights controversies, difficulties, and limitations of such studies. Full article
(This article belongs to the Special Issue Aptamers)
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21 pages, 6544 KiB  
Review
Key Aspects of Nucleic Acid Library Design for in Vitro Selection
by Maria A. Vorobyeva, Anna S. Davydova, Pavel E. Vorobjev, Dmitrii V. Pyshnyi and Alya G. Venyaminova
Int. J. Mol. Sci. 2018, 19(2), 470; https://doi.org/10.3390/ijms19020470 - 05 Feb 2018
Cited by 50 | Viewed by 6765
Abstract
Nucleic acid aptamers capable of selectively recognizing their target molecules have nowadays been established as powerful and tunable tools for biospecific applications, be it therapeutics, drug delivery systems or biosensors. It is now generally acknowledged that in vitro selection enables one to generate [...] Read more.
Nucleic acid aptamers capable of selectively recognizing their target molecules have nowadays been established as powerful and tunable tools for biospecific applications, be it therapeutics, drug delivery systems or biosensors. It is now generally acknowledged that in vitro selection enables one to generate aptamers to almost any target of interest. However, the success of selection and the affinity of the resulting aptamers depend to a large extent on the nature and design of an initial random nucleic acid library. In this review, we summarize and discuss the most important features of the design of nucleic acid libraries for in vitro selection such as the nature of the library (DNA, RNA or modified nucleotides), the length of a randomized region and the presence of fixed sequences. We also compare and contrast different randomization strategies and consider computer methods of library design and some other aspects. Full article
(This article belongs to the Special Issue Aptamers)
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1509 KiB  
Review
Light-Up RNA Aptamers and Their Cognate Fluorogens: From Their Development to Their Applications
by Farah Bouhedda, Alexis Autour and Michael Ryckelynck
Int. J. Mol. Sci. 2018, 19(1), 44; https://doi.org/10.3390/ijms19010044 - 23 Dec 2017
Cited by 76 | Viewed by 11063
Abstract
An RNA-based fluorogenic module consists of a light-up RNA aptamer able to specifically interact with a fluorogen to form a fluorescent complex. Over the past decade, significant efforts have been devoted to the development of such modules, which now cover the whole visible [...] Read more.
An RNA-based fluorogenic module consists of a light-up RNA aptamer able to specifically interact with a fluorogen to form a fluorescent complex. Over the past decade, significant efforts have been devoted to the development of such modules, which now cover the whole visible spectrum, as well as to their engineering to serve in a wide range of applications. In this review, we summarize the different strategies used to develop each partner (the fluorogen and the light-up RNA aptamer) prior to giving an overview of their applications that range from live-cell RNA imaging to the set-up of high-throughput drug screening pipelines. We then conclude with a critical discussion on the current limitations of these modules and how combining in vitro selection with screening approaches may help develop even better molecules. Full article
(This article belongs to the Special Issue Aptamers)
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3356 KiB  
Review
Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery
by Ulrich Hahn
Int. J. Mol. Sci. 2017, 18(12), 2641; https://doi.org/10.3390/ijms18122641 - 06 Dec 2017
Cited by 12 | Viewed by 5614
Abstract
Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 [...] Read more.
Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld. Full article
(This article belongs to the Special Issue Aptamers)
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1270 KiB  
Review
Aptamers and Glioblastoma: Their Potential Use for Imaging and Therapeutic Applications
by Emma M. Hays, Wei Duan and Sarah Shigdar
Int. J. Mol. Sci. 2017, 18(12), 2576; https://doi.org/10.3390/ijms18122576 - 30 Nov 2017
Cited by 29 | Viewed by 5164
Abstract
Glioblastoma is a highly aggressive primary brain tumour, renowned for its infiltrative growth and varied genetic profiles. The current treatment options are insufficient, and their off-target effects greatly reduce patient quality of life. The major challenge in improving glioblastoma diagnosis and treatment involves [...] Read more.
Glioblastoma is a highly aggressive primary brain tumour, renowned for its infiltrative growth and varied genetic profiles. The current treatment options are insufficient, and their off-target effects greatly reduce patient quality of life. The major challenge in improving glioblastoma diagnosis and treatment involves the development of a targeted imaging and drug delivery platform, capable of circumventing the blood brain barrier and specifically targeting glioblastoma tumours. The unique properties of aptamers demonstrate their capability of bridging the gap to the development of successful diagnosis and treatment options, where antibodies have previously failed. Aptamers possess many characteristics that make them an ideal novel imaging and therapeutic agent for the treatment of glioblastoma and other brain malignancies, and are likely to provide patients with a better standard of care and improved quality of life. Their target sensitivity, selective nature, ease of modification and low immunogenicity make them an ideal drug-delivery platform. This review article summarises the aptamers previously generated against glioblastoma cells or its identified biomarkers, and their potential application in diagnosis and therapeutic targeting of glioblastoma tumours. Full article
(This article belongs to the Special Issue Aptamers)
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3391 KiB  
Review
Aptamer Bioinformatics
by Andrew B. Kinghorn, Lewis A. Fraser, Shaolin Liang, Simon Chi-Chin Shiu and Julian A. Tanner
Int. J. Mol. Sci. 2017, 18(12), 2516; https://doi.org/10.3390/ijms18122516 - 24 Nov 2017
Cited by 102 | Viewed by 13770
Abstract
Aptamers are short nucleic acid sequences capable of specific, high-affinity molecular binding. They are isolated via SELEX (Systematic Evolution of Ligands by Exponential Enrichment), an evolutionary process that involves iterative rounds of selection and amplification before sequencing and aptamer characterization. As aptamers are [...] Read more.
Aptamers are short nucleic acid sequences capable of specific, high-affinity molecular binding. They are isolated via SELEX (Systematic Evolution of Ligands by Exponential Enrichment), an evolutionary process that involves iterative rounds of selection and amplification before sequencing and aptamer characterization. As aptamers are genetic in nature, bioinformatic approaches have been used to improve both aptamers and their selection. This review will discuss the advancements made in several enclaves of aptamer bioinformatics, including simulation of aptamer selection, fragment-based aptamer design, patterning of libraries, identification of lead aptamers from high-throughput sequencing (HTS) data and in silico aptamer optimization. Full article
(This article belongs to the Special Issue Aptamers)
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2888 KiB  
Review
Computational Methods for Modeling Aptamers and Designing Riboswitches
by Sha Gong, Yanli Wang, Zhen Wang and Wenbing Zhang
Int. J. Mol. Sci. 2017, 18(11), 2442; https://doi.org/10.3390/ijms18112442 - 17 Nov 2017
Cited by 29 | Viewed by 6109
Abstract
Riboswitches, which are located within certain noncoding RNA region perform functions as genetic “switches”, regulating when and where genes are expressed in response to certain ligands. Understanding the numerous functions of riboswitches requires computation models to predict structures and structural changes of the [...] Read more.
Riboswitches, which are located within certain noncoding RNA region perform functions as genetic “switches”, regulating when and where genes are expressed in response to certain ligands. Understanding the numerous functions of riboswitches requires computation models to predict structures and structural changes of the aptamer domains. Although aptamers often form a complex structure, computational approaches, such as RNAComposer and Rosetta, have already been applied to model the tertiary (three-dimensional (3D)) structure for several aptamers. As structural changes in aptamers must be achieved within the certain time window for effective regulation, kinetics is another key point for understanding aptamer function in riboswitch-mediated gene regulation. The coarse-grained self-organized polymer (SOP) model using Langevin dynamics simulation has been successfully developed to investigate folding kinetics of aptamers, while their co-transcriptional folding kinetics can be modeled by the helix-based computational method and BarMap approach. Based on the known aptamers, the web server Riboswitch Calculator and other theoretical methods provide a new tool to design synthetic riboswitches. This review will represent an overview of these computational methods for modeling structure and kinetics of riboswitch aptamers and for designing riboswitches. Full article
(This article belongs to the Special Issue Aptamers)
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2969 KiB  
Review
Nucleic Acid Aptamers: Emerging Applications in Medical Imaging, Nanotechnology, Neurosciences, and Drug Delivery
by Pascal Röthlisberger, Cécile Gasse and Marcel Hollenstein
Int. J. Mol. Sci. 2017, 18(11), 2430; https://doi.org/10.3390/ijms18112430 - 16 Nov 2017
Cited by 67 | Viewed by 9133
Abstract
Recent progresses in organic chemistry and molecular biology have allowed the emergence of numerous new applications of nucleic acids that markedly deviate from their natural functions. Particularly, DNA and RNA molecules—coined aptamers—can be brought to bind to specific targets with high affinity and [...] Read more.
Recent progresses in organic chemistry and molecular biology have allowed the emergence of numerous new applications of nucleic acids that markedly deviate from their natural functions. Particularly, DNA and RNA molecules—coined aptamers—can be brought to bind to specific targets with high affinity and selectivity. While aptamers are mainly applied as biosensors, diagnostic agents, tools in proteomics and biotechnology, and as targeted therapeutics, these chemical antibodies slowly begin to be used in other fields. Herein, we review recent progress on the use of aptamers in the construction of smart DNA origami objects and MRI and PET imaging agents. We also describe advances in the use of aptamers in the field of neurosciences (with a particular emphasis on the treatment of neurodegenerative diseases) and as drug delivery systems. Lastly, the use of chemical modifications, modified nucleoside triphosphate particularly, to enhance the binding and stability of aptamers is highlighted. Full article
(This article belongs to the Special Issue Aptamers)
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1240 KiB  
Review
Aptamers for DNA Damage and Repair
by Maureen McKeague
Int. J. Mol. Sci. 2017, 18(10), 2212; https://doi.org/10.3390/ijms18102212 - 22 Oct 2017
Cited by 8 | Viewed by 10063
Abstract
DNA is damaged on a daily basis, which can lead to heritable mutations and the activation of proto-oncogenes. Therefore, DNA damage and repair are critical risk factors in cancer, aging and disease, and are the underlying bases of most frontline cancer therapies. Much [...] Read more.
DNA is damaged on a daily basis, which can lead to heritable mutations and the activation of proto-oncogenes. Therefore, DNA damage and repair are critical risk factors in cancer, aging and disease, and are the underlying bases of most frontline cancer therapies. Much of our current understanding of the mechanisms that maintain DNA integrity has been obtained using antibody-based assays. The oligonucleotide equivalents of antibodies, known as aptamers, have emerged as potential molecular recognition rivals. Aptamers possess several ideal properties including chemical stability, in vitro selection and lack of batch-to-batch variability. These properties have motivated the incorporation of aptamers into a wide variety of analytical, diagnostic, research and therapeutic applications. However, their use in DNA repair studies and DNA damage therapies is surprisingly un-tapped. This review presents an overview of the progress in selecting and applying aptamers for DNA damage and repair research. Full article
(This article belongs to the Special Issue Aptamers)
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3606 KiB  
Review
Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes
by Shuaijian Ni, Houzong Yao, Lili Wang, Jun Lu, Feng Jiang, Aiping Lu and Ge Zhang
Int. J. Mol. Sci. 2017, 18(8), 1683; https://doi.org/10.3390/ijms18081683 - 02 Aug 2017
Cited by 217 | Viewed by 13385
Abstract
Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic [...] Read more.
Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic applications. In this review, we will discuss methods to conquer these challenges and highlight recent developments of chemical modifications and technological advances that may enable early aptamers to be translated into clinical therapeutics. Full article
(This article belongs to the Special Issue Aptamers)
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872 KiB  
Review
Unraveling Prion Protein Interactions with Aptamers and Other PrP-Binding Nucleic Acids
by Bruno Macedo and Yraima Cordeiro
Int. J. Mol. Sci. 2017, 18(5), 1023; https://doi.org/10.3390/ijms18051023 - 17 May 2017
Cited by 32 | Viewed by 5801
Abstract
Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative disorders that affect humans and other mammals. The etiologic agents common to these diseases are misfolded conformations of the prion protein (PrP). The molecular mechanisms that trigger the structural conversion of the normal cellular [...] Read more.
Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative disorders that affect humans and other mammals. The etiologic agents common to these diseases are misfolded conformations of the prion protein (PrP). The molecular mechanisms that trigger the structural conversion of the normal cellular PrP (PrPC) into the pathogenic conformer (PrPSc) are still poorly understood. It is proposed that a molecular cofactor would act as a catalyst, lowering the activation energy of the conversion process, therefore favoring the transition of PrPC to PrPSc. Several in vitro studies have described physical interactions between PrP and different classes of molecules, which might play a role in either PrP physiology or pathology. Among these molecules, nucleic acids (NAs) are highlighted as potential PrP molecular partners. In this context, the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology has proven extremely valuable to investigate PrP–NA interactions, due to its ability to select small nucleic acids, also termed aptamers, that bind PrP with high affinity and specificity. Aptamers are single-stranded DNA or RNA oligonucleotides that can be folded into a wide range of structures (from harpins to G-quadruplexes). They are selected from a nucleic acid pool containing a large number (1014–1016) of random sequences of the same size (~20–100 bases). Aptamers stand out because of their potential ability to bind with different affinities to distinct conformations of the same protein target. Therefore, the identification of high-affinity and selective PrP ligands may aid the development of new therapies and diagnostic tools for TSEs. This review will focus on the selection of aptamers targeted against either full-length or truncated forms of PrP, discussing the implications that result from interactions of PrP with NAs, and their potential advances in the studies of prions. We will also provide a critical evaluation, assuming the advantages and drawbacks of the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technique in the general field of amyloidogenic proteins. Full article
(This article belongs to the Special Issue Aptamers)
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