Special Issue "Potential of the Aptamers to Fill Therapeutic and Diagnostic Gaps"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: 31 October 2021.

Special Issue Editors

Dr. Cristina Romero-López
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Guest Editor
Department of Molecular Biology, Instituto de Parasitología y Biomedicina López-Neyra (IPBLN-CSIC), PTS Granada, Av. Conocimiento, 18016 Armilla, Granada, Spain
Interests: RNA structural biology; Aptamers; Viral RNA genomes; Functional RNA
Special Issues and Collections in MDPI journals
Dr. Alfredo Berzal-Herranz
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Guest Editor
Department of Molecular Biology, Instituto de Parasitología y Biomedicina López-Neyra, (IPBLN-CSIC), PTS Granada, Av del Conocimiento 17, 18016 Granada, Spain
Interests: structure-function of RNA; aptamers; antisense; ribozymes; viral RNA genomes; RNA as tool; therapeutic RNAs
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

We are glad to invite authors to submit original manuscripts in the field of medicinal aptamers. Aptamers are short, functional oligonucleotides able to recognize, in a specific way, a wide variety of molecular targets. These targets range from ions or small compounds to whole viruses or even cells. Aptamers are isolated from selection experiments, either in vitro, ex vivo, or both, by virtue of their affinity and specificity for the desired target. Such properties are intrinsically related to the aptamer three-dimensional folding, which operates as a template to guide the identification of a precise target, in a similar way to the key and lock model described for protein enzymes.

The potential of aptamers as molecular tools in multiple areas, such as food safety or environmental preservation, has been largely proposed. However, major investigations in the aptamers field are related to their biomedical exploitation, thus opening a new exciting field for the development of novel diagnostic and therapeutic aptamers-based strategies. Moreover, they have enabled significant advances in basic research.

This Special Issue aims to collect both review and original research articles that present the current state-of-the-art of aptamers in clinics, either as diagnostic or therapeutic agents. Reports on technology applications for the development of aptamers-based diagnostic platforms are also welcome. Their invaluable contribution to biomedical investigations can also be discussed.

Dr. Cristina Romero-López
Dr. Alfredo Berzal-Herranz
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • aptamer
  • nucleic acid tools
  • RNA aptamers
  • DNA aptamers
  • peptide aptamers
  • Spiegelmers
  • SELEX
  • aptamer conjugates
  • diagnostic aptamers
  • therapeutic aptamers
  • aptamers pharmacology
  • antiviral aptamers
  • anticancer aptamers
  • aptamer imaging

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Published Papers (6 papers)

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Research

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Article
DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells
Pharmaceuticals 2021, 14(5), 473; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050473 - 17 May 2021
Viewed by 669
Abstract
Vaccinia-related kinase (VRK) 1 is a serin/threonine kinase that plays an important role in DNA damage response (DDR), phosphorylating some proteins involved in this process such as 53BP1, NBS1 or H2AX, and in the cell cycle progression. In addition, VRK1 is overexpressed in [...] Read more.
Vaccinia-related kinase (VRK) 1 is a serin/threonine kinase that plays an important role in DNA damage response (DDR), phosphorylating some proteins involved in this process such as 53BP1, NBS1 or H2AX, and in the cell cycle progression. In addition, VRK1 is overexpressed in many cancer types and its correlation with poor prognosis has been determined, showing VRK1 as a new therapeutic target in oncology. Using in vitro selection, high-affinity DNA aptamers to VRK1 were selected from a library of ssDNA. Selection was monitored using the enzyme-linked oligonucleotide assay (ELONA), and the selected aptamer population was cloned and sequenced. Three aptamers were selected and characterized. These aptamers recognized the protein kinase VRK1 with an affinity in the nanomolar range and showed a high sensibility. Moreover, the treatment of the MCF7 breast cell line with these aptamers resulted in a decrease in cyclin D1 levels, and an inhibition of cell cycle progression by G1 phase arrest, which induced apoptosis in cells. These results suggest that these aptamers are specific inhibitors of VRK1 that might be developed as potential drugs for the treatment of cancer. Full article
(This article belongs to the Special Issue Potential of the Aptamers to Fill Therapeutic and Diagnostic Gaps)
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Article
Improving Breast Cancer Treatment Specificity Using Aptamers Obtained by 3D Cell-SELEX
Pharmaceuticals 2021, 14(4), 349; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040349 - 09 Apr 2021
Viewed by 603
Abstract
Three-dimensional spheroids of non-malignant MCF10A and malignant SKBR3 breast cells were used for subsequent 3D Cell-SELEX to generate aptamers for specific binding and treatment of breast cancer cells. Using 3D Cell-SELEX combined with Next-Generation Sequencing and bioinformatics, ten abundant aptamer families with specific [...] Read more.
Three-dimensional spheroids of non-malignant MCF10A and malignant SKBR3 breast cells were used for subsequent 3D Cell-SELEX to generate aptamers for specific binding and treatment of breast cancer cells. Using 3D Cell-SELEX combined with Next-Generation Sequencing and bioinformatics, ten abundant aptamer families with specific structures were identified that selectively bind to SKBR3, and not to MCF10A cells. Multivalent aptamer polymers were synthesized by co-polymerization and analyzed for binding performance as well as therapeutic efficacy. Binding performance was determined by confocal fluorescence imaging and revealed specific binding and efficient internalization of aptamer polymers into SKBR3 spheroids. For therapeutic purposes, DNA sequences that intercalate the cytotoxic drug doxorubicin were co-polymerized into the aptamer polymers. Viability tests show that the drug-loaded polymers are specific and effective in killing SKBR3 breast cancer cells. Thus, the 3D-selected aptamers enhanced the specificity of doxorubicin against malignant over non-malignant breast cells. The innovative modular DNA aptamer platform based on 3D Cell SELEX and polymer multivalency holds great promise for diagnostics and treatment of breast cancer. Full article
(This article belongs to the Special Issue Potential of the Aptamers to Fill Therapeutic and Diagnostic Gaps)
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Communication
Remyelination-Promoting DNA Aptamer Conjugate Myaptavin-3064 Binds to Adult Oligodendrocytes In Vitro
Pharmaceuticals 2020, 13(11), 403; https://0-doi-org.brum.beds.ac.uk/10.3390/ph13110403 - 19 Nov 2020
Viewed by 631
Abstract
We previously applied Systematic Evolution of Ligands by EXponential enrichment (SELEX) technology to identify myelin-specific DNA aptamers, using crude mouse central nervous system myelin as bait. This selection identified a 40-nucleotide aptamer (LJM-3064). Multiple biotinylated LJM-3064 molecules were conjugated to a streptavidin core [...] Read more.
We previously applied Systematic Evolution of Ligands by EXponential enrichment (SELEX) technology to identify myelin-specific DNA aptamers, using crude mouse central nervous system myelin as bait. This selection identified a 40-nucleotide aptamer (LJM-3064). Multiple biotinylated LJM-3064 molecules were conjugated to a streptavidin core to mimic a multimeric immunoglobulin M (IgM) antibody, generating 3064-BS-streptavidin (Myaptavin-3064). We previously showed that Myaptavin-3064 induces remyelination in the Theiler’s murine encephalomyelitis virus (TMEV) model of chronic spinal cord demyelination. While details of target binding and the mechanism of action remain unclear, we hypothesized that Myaptavin-3064 induces remyelination by binding to oligodendrocytes (OLs). We now report the results of binding assays using the human oligodendroglioma (HOG) cell line, applying both flow cytometry and immunocytochemistry (IC) to assay aptamer conjugate binding to cells. IC assays were applied to compare aptamer conjugate binding to primary embryonic mouse mixed cortical cultures and primary adult rat mixed glial cultures. We show that Myaptavin-3064 binds to HOG cells, with increased binding upon differentiation. In contrast, a negative control aptamer conjugate, 3060-BS, which did not promote central nervous system (CNS) remyelination, does not bind to HOG cells. Myaptavin-3064 did not bind to lung (L2) or kidney (BHK) cell lines. Total internal reflection fluorescence (TIRF) imaging indicates that Myaptavin-3064 binds at the cell membrane of live cells. In addition to HOG cells, Myaptavin-3064 binds to adult rat OLs, but not to embryonic mouse mixed cortical cultures. These data support the hypothesis that Myaptavin-3064 binds to a surface molecule on both rodent and human OLs in a manner that triggers a remyelination signal pathway. Full article
(This article belongs to the Special Issue Potential of the Aptamers to Fill Therapeutic and Diagnostic Gaps)
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Review

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Review
Aptamer Applications in Emerging Viral Diseases
Pharmaceuticals 2021, 14(7), 622; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070622 - 28 Jun 2021
Viewed by 714
Abstract
Aptamers are single-stranded DNA or RNA molecules which are submitted to a process denominated SELEX. SELEX uses reiterative screening of a random oligonucleotide library to identify high-affinity binders to a chosen target, which may be a peptide, protein, or entire cells or viral [...] Read more.
Aptamers are single-stranded DNA or RNA molecules which are submitted to a process denominated SELEX. SELEX uses reiterative screening of a random oligonucleotide library to identify high-affinity binders to a chosen target, which may be a peptide, protein, or entire cells or viral particles. Aptamers can rival antibodies in target recognition, and benefit from their non-proteic nature, ease of modification, increased stability, and pharmacokinetic properties. This turns them into ideal candidates for diagnostic as well as therapeutic applications. Here, we review the recent accomplishments in the development of aptamers targeting emerging viral diseases, with emphasis on recent findings of aptamers binding to coronaviruses. We focus on aptamer development for diagnosis, including biosensors, in addition to aptamer modifications for stabilization in body fluids and tissue penetration. Such aptamers are aimed at in vivo diagnosis and treatment, such as quantification of viral load and blocking host cell invasion, virus assembly, or replication, respectively. Although there are currently no in vivo applications of aptamers in combating viral diseases, such strategies are promising for therapy development in the future. Full article
(This article belongs to the Special Issue Potential of the Aptamers to Fill Therapeutic and Diagnostic Gaps)
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Review
Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors
Pharmaceuticals 2021, 14(6), 554; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060554 - 10 Jun 2021
Viewed by 799
Abstract
Vectors developed from adeno-associated virus (AAV) are powerful tools for in vivo transgene delivery in both humans and animal models, and several AAV-delivered gene therapies are currently approved for clinical use. However, AAV-mediated gene therapy still faces several challenges, including limited vector packaging [...] Read more.
Vectors developed from adeno-associated virus (AAV) are powerful tools for in vivo transgene delivery in both humans and animal models, and several AAV-delivered gene therapies are currently approved for clinical use. However, AAV-mediated gene therapy still faces several challenges, including limited vector packaging capacity and the need for a safe, effective method for controlling transgene expression during and after delivery. Riboswitches, RNA elements which control gene expression in response to ligand binding, are attractive candidates for regulating expression of AAV-delivered transgene therapeutics because of their small genomic footprints and non-immunogenicity compared to protein-based expression control systems. In addition, the ligand-sensing aptamer domains of many riboswitches can be exchanged in a modular fashion to allow regulation by a variety of small molecules, proteins, and oligonucleotides. Riboswitches have been used to regulate AAV-delivered transgene therapeutics in animal models, and recently developed screening and selection methods allow rapid isolation of riboswitches with novel ligands and improved performance in mammalian cells. This review discusses the advantages of riboswitches in the context of AAV-delivered gene therapy, the subsets of riboswitch mechanisms which have been shown to function in human cells and animal models, recent progress in riboswitch isolation and optimization, and several examples of AAV-delivered therapeutic systems which might be improved by riboswitch regulation. Full article
(This article belongs to the Special Issue Potential of the Aptamers to Fill Therapeutic and Diagnostic Gaps)
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Review
Logic Gates Based on DNA Aptamers
Pharmaceuticals 2020, 13(11), 417; https://0-doi-org.brum.beds.ac.uk/10.3390/ph13110417 - 23 Nov 2020
Cited by 2 | Viewed by 833
Abstract
DNA bio-computing is an emerging trend in modern science that is based on interactions among biomolecules. Special types of DNAs are aptamers that are capable of selectively forming complexes with target compounds. This review is devoted to a discussion of logic gates based [...] Read more.
DNA bio-computing is an emerging trend in modern science that is based on interactions among biomolecules. Special types of DNAs are aptamers that are capable of selectively forming complexes with target compounds. This review is devoted to a discussion of logic gates based on aptamers for the purposes of medicine and analytical chemistry. The review considers different approaches to the creation of logic gates and identifies the general algorithms of their creation, as well as describes the methods of obtaining an output signal which can be divided into optical and electrochemical. Aptameric logic gates based on DNA origami and DNA nanorobots are also shown. The information presented in this article can be useful when creating new logic gates using existing aptamers and aptamers that will be selected in the future. Full article
(This article belongs to the Special Issue Potential of the Aptamers to Fill Therapeutic and Diagnostic Gaps)
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