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Biomedicines
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Engineering Aptamers for Biomedical Applications
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Engineering Aptamers for Biomedical Applications

A special issue of Biomedicines (ISSN 2227-9059).

Deadline for manuscript submissions: closed (31 March 2018) | Viewed by 56200

Special Issue Editor

Dr. Vittorio de Franciscis

E-Mail Website
Guest Editor
Istituto per l'Endocrinologia e Oncologia Sperimentale "G. Salvatore", Via Tommaso De Amicis 95 Via S. Pansini 5, 80145 Naples, Italy
Interests: RNA therapeutics; delivery of nucleic acid therapeutics; aptamer; tumor microenvironment; signal transduction; microRNA; targeted therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, “Engineering Aptamers for Biomedical Applications”, will mainly focus on the more recent advances in the development of highly stable and specific aptamers suitable as therapeutic and diagnostic agents.

The introduction of modifications in the nucleic acids backbone, the expansion of genetic variability in nucleobases and the generation of enzymes able to catalyze the synthesis of modified aptamers is revealing as invaluable advantage in the design of aptamer ligands in biomedicine. Aptamers obtained with nucleic acid variants exhibit high stability in circulating fluids, target binding affinity and specificity thus potentially improving their applicability as therapeutics and/or as diagnostic tools.

We cordially invite authors in the field to submit original research or review articles pertaining to this important and fast-progressing field of biomedicine.

Dr. Vittorio de Franciscis
Guest Editor

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 submissions that pass pre-check are 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. Biomedicines 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 2600 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 probes and therapeutics
  • biosensors
  • ODN nanotechnology
  • ribozymes/DNAzymes evolution
  • combinatorial therapy
  • molecular evolution
  • expanded genetic

Published Papers (7 papers)

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Review

13 pages, 2231 KiB  
Review
Artificially Expanded Genetic Information Systems for New Aptamer Technologies
by Elisa Biondi and Steven A. Benner
Biomedicines 2018, 6(2), 53; https://doi.org/10.3390/biomedicines6020053 - 09 May 2018
Cited by 53 | Viewed by 5828
Abstract
Directed evolution was first applied to diverse libraries of DNA and RNA molecules a quarter century ago in the hope of gaining technology that would allow the creation of receptors, ligands, and catalysts on demand. Despite isolated successes, the outputs of this technology [...] Read more.
Directed evolution was first applied to diverse libraries of DNA and RNA molecules a quarter century ago in the hope of gaining technology that would allow the creation of receptors, ligands, and catalysts on demand. Despite isolated successes, the outputs of this technology have been somewhat disappointing, perhaps because the four building blocks of standard DNA and RNA have too little functionality to have versatile binding properties, and offer too little information density to fold unambiguously. This review covers the recent literature that seeks to create an improved platform to support laboratory Darwinism, one based on an artificially expanded genetic information system (AEGIS) that adds independently replicating nucleotide “letters” to the evolving “alphabet”. Full article
(This article belongs to the Special Issue Engineering Aptamers for Biomedical Applications)
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3981 KiB  
Review
Engineered Aptamers to Probe Molecular Interactions on the Cell Surface
by Sana Batool, Sanam Bhandari, Shanell George, Precious Okeoma, Nabeela Van, Hazan E. Zümrüt and Prabodhika Mallikaratchy
Biomedicines 2017, 5(3), 54; https://doi.org/10.3390/biomedicines5030054 - 29 Aug 2017
Cited by 16 | Viewed by 5399
Abstract
Significant progress has been made in understanding the nature of molecular interactions on the cell membrane. To decipher such interactions, molecular scaffolds can be engineered as a tool to modulate these events as they occur on the cell membrane. To guarantee reliability, scaffolds [...] Read more.
Significant progress has been made in understanding the nature of molecular interactions on the cell membrane. To decipher such interactions, molecular scaffolds can be engineered as a tool to modulate these events as they occur on the cell membrane. To guarantee reliability, scaffolds that function as modulators of cell membrane events must be coupled to a targeting moiety with superior chemical versatility. In this regard, nucleic acid aptamers are a suitable class of targeting moieties. Aptamers are inherently chemical in nature, allowing extensive site-specific chemical modification to engineer sensing molecules. Aptamers can be easily selected using a simple laboratory-based in vitro evolution method enabling the design and development of aptamer-based functional molecular scaffolds against wide range of cell surface molecules. This article reviews the application of aptamers as monitors and modulators of molecular interactions on the mammalian cell surface with the aim of increasing our understanding of cell-surface receptor response to external stimuli. The information gained from these types of studies could eventually prove useful in engineering improved medical diagnostics and therapeutics. Full article
(This article belongs to the Special Issue Engineering Aptamers for Biomedical Applications)
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2528 KiB  
Review
Toward the Selection of Cell Targeting Aptamers with Extended Biological Functionalities to Facilitate Endosomal Escape of Cargoes
by Kwaku D. Tawiah, David Porciani and Donald H. Burke
Biomedicines 2017, 5(3), 51; https://doi.org/10.3390/biomedicines5030051 - 24 Aug 2017
Cited by 32 | Viewed by 7868
Abstract
Over the past decades there have been exciting and rapid developments of highly specific molecules to bind cancer antigens that are overexpressed on the surfaces of malignant cells. Nanomedicine aims to exploit these ligands to generate nanoscale platforms for targeted cancer therapy, and [...] Read more.
Over the past decades there have been exciting and rapid developments of highly specific molecules to bind cancer antigens that are overexpressed on the surfaces of malignant cells. Nanomedicine aims to exploit these ligands to generate nanoscale platforms for targeted cancer therapy, and to do so with negligible off-target effects. Aptamers are structured nucleic acids that bind to defined molecular targets ranging from small molecules and proteins to whole cells or viruses. They are selected through an iterative process of amplification and enrichment called SELEX (systematic evolution of ligands by exponential enrichment), in which a combinatorial oligonucleotide library is exposed to the target of interest for several repetitive rounds. Nucleic acid ligands able to bind and internalize into malignant cells have been extensively used as tools for targeted delivery of therapeutic payloads both in vitro and in vivo. However, current cell targeting aptamer platforms suffer from limitations that have slowed their translation to the clinic. This is especially true for applications in which the cargo must reach the cytosol to exert its biological activity, as only a small percentage of the endocytosed cargo is typically able to translocate into the cytosol. Innovative technologies and selection strategies are required to enhance cytoplasmic delivery. In this review, we describe current selection methods used to generate aptamers that target cancer cells, and we highlight some of the factors that affect productive endosomal escape of cargoes. We also give an overview of the most promising strategies utilized to improve and monitor endosomal escape of therapeutic cargoes. The methods we highlight exploit tools and technologies that can potentially be incorporated in the SELEX process. Innovative selection protocols may identify aptamers with extended biological functionalities that allow effective cytosolic translocation of therapeutics. This in turn may facilitate successful translation of these platforms into clinical applications. Full article
(This article belongs to the Special Issue Engineering Aptamers for Biomedical Applications)
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Graphical abstract

5880 KiB  
Review
Aptamer Cell-Based Selection: Overview and Advances
by Silvia Catuogno and Carla Lucia Esposito
Biomedicines 2017, 5(3), 49; https://doi.org/10.3390/biomedicines5030049 - 14 Aug 2017
Cited by 64 | Viewed by 8577
Abstract
Aptamers are high affinity single-stranded DNA/RNA molecules, produced by a combinatorial procedure named SELEX (Systematic Evolution of Ligands by Exponential enrichment), that are emerging as promising diagnostic and therapeutic tools. Among selection strategies, procedures using living cells as complex targets (referred as “cell-SELEX”) [...] Read more.
Aptamers are high affinity single-stranded DNA/RNA molecules, produced by a combinatorial procedure named SELEX (Systematic Evolution of Ligands by Exponential enrichment), that are emerging as promising diagnostic and therapeutic tools. Among selection strategies, procedures using living cells as complex targets (referred as “cell-SELEX”) have been developed as an effective mean to generate aptamers for heavily modified cell surface proteins, assuring the binding of the target in its native conformation. Here we give an up-to-date overview on cell-SELEX technology, discussing the most recent advances with a particular focus on cancer cell targeting. Examples of the different protocol applications and post-SELEX strategies will be briefly outlined. Full article
(This article belongs to the Special Issue Engineering Aptamers for Biomedical Applications)
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Graphical abstract

2437 KiB  
Review
Aptamer-siRNA Chimeras: Discovery, Progress, and Future Prospects
by Sven Kruspe and Paloma H. Giangrande
Biomedicines 2017, 5(3), 45; https://doi.org/10.3390/biomedicines5030045 - 09 Aug 2017
Cited by 74 | Viewed by 9628
Abstract
Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery tools for many therapeutic oligonucleotide-based drugs, including small interfering RNAs (siRNAs). In this review, we summarize recent progress in the aptamer selection technology that has made possible the identification of cell-specific, cell-internalizing aptamers [...] Read more.
Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery tools for many therapeutic oligonucleotide-based drugs, including small interfering RNAs (siRNAs). In this review, we summarize recent progress in the aptamer selection technology that has made possible the identification of cell-specific, cell-internalizing aptamers for the cell-targeted delivery of therapeutic oligonucleotides. In addition, we review the original, proof-of-concept aptamer-siRNA delivery studies and discuss recent advances in aptamer-siRNA conjugate designs for applications ranging from cancer therapy to the development of targeted antivirals. Challenges and prospects of aptamer-targeted siRNA drugs for clinical development are further highlighted. Full article
(This article belongs to the Special Issue Engineering Aptamers for Biomedical Applications)
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Graphical abstract

2564 KiB  
Review
Development of Phosphorothioate DNA and DNA Thioaptamers
by David E. Volk and Ganesh L. R. Lokesh
Biomedicines 2017, 5(3), 41; https://doi.org/10.3390/biomedicines5030041 - 13 Jul 2017
Cited by 52 | Viewed by 8466
Abstract
Nucleic acid aptamers are short RNA- or DNA-based affinity reagents typically selected from combinatorial libraries to bind to a specific target such as a protein, a small molecule, whole cells or even animals. Aptamers have utility in the development of diagnostic, imaging and [...] Read more.
Nucleic acid aptamers are short RNA- or DNA-based affinity reagents typically selected from combinatorial libraries to bind to a specific target such as a protein, a small molecule, whole cells or even animals. Aptamers have utility in the development of diagnostic, imaging and therapeutic applications due to their size, physico-chemical nature and ease of synthesis and modification to suit the application. A variety of oligonucleotide modifications have been used to enhance the stability of aptamers from nuclease degradation in vivo. The non-bridging oxygen atoms of the phosphodiester backbones of RNA and DNA aptamers can be substituted with one or two sulfur atoms, resulting in thioaptamers with phosphorothioate or phosphorodithioate linkages, respectively. Such thioaptamers are known to have increased binding affinity towards their target, as well as enhanced resistance to nuclease degradation. In this review, we discuss the development of phosphorothioate chemistry and thioaptamers, with a brief review of selection methods. Full article
(This article belongs to the Special Issue Engineering Aptamers for Biomedical Applications)
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Graphical abstract

1233 KiB  
Review
Aptamer Technology: Adjunct Therapy for Malaria
by Nik Abdul Aziz Nik Kamarudin, Nurul Adila Mohammed and Khairul Mohd Fadzli Mustaffa
Biomedicines 2017, 5(1), 1; https://doi.org/10.3390/biomedicines5010001 - 04 Jan 2017
Cited by 10 | Viewed by 9397
Abstract
Malaria is a life-threatening parasitic infection occurring in the endemic areas, primarily in children under the age of five, pregnant women, and patients with human immunodeficiency virus and acquired immunodeficiency syndrome (HIV)/(AIDS) as well as non-immune individuals. The cytoadherence of infected erythrocytes (IEs) [...] Read more.
Malaria is a life-threatening parasitic infection occurring in the endemic areas, primarily in children under the age of five, pregnant women, and patients with human immunodeficiency virus and acquired immunodeficiency syndrome (HIV)/(AIDS) as well as non-immune individuals. The cytoadherence of infected erythrocytes (IEs) to the host endothelial surface receptor is a known factor that contributes to the increased prevalence of severe malaria cases due to the accumulation of IEs, mainly in the brain and other vital organs. Therefore, further study is needed to discover a new potential anti-adhesive drug to treat severe malaria thus reducing its mortality rate. In this review, we discuss how the aptamer technology could be applied in the development of a new adjunct therapy for current malaria treatment. Full article
(This article belongs to the Special Issue Engineering Aptamers for Biomedical Applications)
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