Special Issue "Aptamer-Based Therapeutics"
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A special issue of Pharmaceuticals (ISSN 1424-8247).
Deadline for manuscript submissions: 30 June 2013
Special Issue Editor
Guest Editor
Dr. Sotiris Missailidis
Department of Chemistry and Analytical Sciences, The Open University, Walton Hall, Milton Keynes, UK
E-Mail: s.missailidis@open.ac.uk
Interests: pharmacogenomics; molecular recognition; biomarkers; DNA biomimetics; aptamers as DNA targeting; therapeutic and imaging agents; inflammation and cancer; organometallic drug; aptamers as therapeutic and diagnostic agents or as recognition elements in biosensor development
Special Issue Information
Dear Colleagues,
We invite authors to submit papers to Pharmaceuticals in the exciting field of Aptamer research. This special issue is to include original papers and review articles on basic or clinical research on aptamers, including aptamer selection methodologies, aptamer conjugates, aptamer nanoparticles, spiegelmers, peptide aptamers, locked aptamers and different aptamer applications, including applications in diagnostics, imaging, therapy, sensors or other technology development, aptamer pharmacology, biomarker discovery or clinical applications.
Dr. Sotiris Missailidis
Guest Editor
Submission
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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 500 CHF (Swiss Francs).
English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
Keywords
- aptamer Selection
- SELEX
- aptamer conjugates
- aptamer nanoparticles
- spiegelmers
- peptide aptamers
- DNA aptamers
- RNA aptamer
- aptasensors
- photoaptamers
- locked aptamers
- aptamer conjugates
- aptamer nanoparticles
- aptamer diagnostics
- aptamer therapeutics
- aptamer radiopharmaceuticals
- aptamers in oncology
- aptamer metabolism
- aptamer pharmacology
- clinical trials
Published Papers (8 papers)
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Received: 14 January 2011; in revised form: 8 February 2011 / Accepted: 16 February 2011 / Published: 18 February 2011
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Abstract: An evolution of antibiotic-resistant bacteria has resulted in the need for new antibiotics. β-Lactam based drugs are the most predominantly prescribed antibiotics to combat bacterial infections; however, production of β-lactamases, which catalyze the hydrolysis of the β-lactam bond of this class of antibiotics, by pathogenic bacteria such as Bacillus cereus, are rendering them useless. Some inhibitors of β-lactamases have been found, but there are no inhibitors against a class of β-lactamases known as metallo-β-lactamases, and it has been reported that the number of bacteria that produce metallo-β-lactamases is on the rise. Finding inhibitors of metallo-β-lactamases is thus an urgent necessity. One way to approach the problem is by employing the combinatorial method SELEX. The SELEX method is significant in discovering and producing new classes of inhibitors, as well as providing insight into the development of these inhibitors and paves the way for future aptamer applications that further novel drug discovery.
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Received: 28 December 2010; in revised form: 17 January 2011 / Accepted: 11 February 2011 / Published: 10 March 2011
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Abstract: Many genetic and infectious diseases can be targeted at the RNA level as RNA is more accessible than DNA. We seek to develop new approaches for detection and tracking RNA in live cells, which is necessary for RNA-based diagnostics and therapy. We recently described a method for RNA visualization in live bacterial cells based on fluorescent protein complementation [1-3]. The RNA is tagged with an RNA aptamer that binds an RNA-binding protein with high affinity. This RNA-binding protein is expressed as two split fragments fused to the fragments of a split fluorescent protein. In the presence of RNA the fragments of the RNA-binding protein bind the aptamer and bring together the fragments of the fluorescent protein, which results in its re-assembly and fluorescence development [1-3]. Here we describe a new version of the RNA labeling method where fluorescent protein complementation is triggered by paired interactions of two different closely-positioned RNA aptamers with two different RNA-binding viral peptides. The new method, which has been developed in bacteria as a model system, uses a smaller ribonucleoprotein complementation complex, as compared with the method using split RNA-binding protein, and it can potentially be applied to a broad variety of RNA targets in both prokaryotic and eukaryotic cells. We also describe experiments exploring background fluorescence in these RNA detection systems and conditions that improve the signal-to-background ratio.
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Received: 6 July 2011; in revised form: 4 August 2011 / Accepted: 11 August 2011 / Published: 15 August 2011
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Abstract: Aptamers are functional nucleic acid sequences which can bind specific targets. An artificial combinatorial methodology can identify aptamer sequences for any target molecule, from ions to whole cells. Drug delivery systems seek to increase efficacy and reduce side-effects by concentrating the therapeutic agents at specific disease sites in the body. This is generally achieved by specific targeting of inactivated drug molecules. Aptamers which can bind to various cancer cell types selectively and with high affinity have been exploited in a variety of drug delivery systems for therapeutic purposes. Recent progress in selection of cell-specific aptamers has provided new opportunities in targeted drug delivery. Especially functionalization of nanoparticles with such aptamers has drawn major attention in the biosensor and biomedical areas. Moreover, nucleic acids are recognized as an attractive building materials in nanomachines because of their unique molecular recognition properties and structural features. A active controlled delivery of drugs once targeted to a disease site is a major research challenge. Stimuli-responsive gating is one way of achieving controlled release of nanoparticle cargoes. Recent reports incorporate the structural properties of aptamers in controlled release systems of drug delivering nanoparticles. In this review, the strategies for using functional nucleic acids in creating smart drug delivery devices will be explained. The main focus will be on aptamer-incorporated nanoparticle systems for drug delivery purposes in order to assess the future potential of aptamers in the therapeutic area. Special emphasis will be given to the very recent progress in controlled drug release based on molecular gating achieved with aptamers.
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Received: 1 August 2011; in revised form: 2 September 2011 / Accepted: 9 September 2011 / Published: 20 September 2011
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Abstract: Aptamers are nucleic acid-based ligands identified through a process of molecular evolution named SELEX (Systematic Evolution of Ligands by Exponential enrichment). During the last 10-15 years, numerous aptamers have been developed specifically against targets present on or associated with the surface of human cells or infectious pathogens such as viruses, bacteria, fungi or parasites. Several of the aptamers have been described as potent probes, rivalling antibodies, for use in flow cytometry or microscopy. Some have also been used as drugs by inhibiting or activating functions of their targets in a manner similar to neutralizing or agonistic antibodies. Additionally, it is straightforward to conjugate aptamers to other agents without losing their affinity and they have successfully been used in vitro and in vivo to deliver drugs, siRNA, nanoparticles or contrast agents to target cells. Hence, aptamers identified against cell surface biomarkers represent a promising class of ligands. This review presents the different strategies of SELEX that have been developed to identify aptamers for cell surface-associated proteins as well as some of the methods that are used to study their binding on living cells.
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Received: 22 September 2011; in revised form: 13 October 2011 / Accepted: 24 October 2011 / Published: 27 October 2011
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Abstract: RNA-based approaches are among the most promising strategies aimed at developing safer and more effective therapeutics. RNA therapeutics include small non-coding miRNAs, small interfering RNA, RNA aptamers and more recently, small activating RNAs. However, major barriers exist to the use of RNAs as therapeutics such as resistance to nucleases present in biological fluids, poor chemical stability, need of specific cell targeted delivery and easy entry into the cell. Such issues have been addressed by several recent reports that show the possibility of introducing chemical modifications in small RNAs to stabilize the molecular conformation and increase by several fold their integrity, while still preserving the functional activity. Further, several aptamers have been developed as excellent candidates for the specific recognition of cell surface targets. In the last few years, by taking advantage of recent advances in the small RNA field, molecular bioconjugates have been designed that permit specific targeting and may act as cargoes for cell internalization of small RNAs acting on gene expression that will be discussed in this review.
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Received: 28 November 2011; in revised form: 15 December 2011 / Accepted: 22 December 2011 / Published: 28 December 2011
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Abstract: Hepatitis C virus (HCV) replication is dependent on the existence of several highly conserved functional genomic RNA domains. The cis-acting replication element (CRE), located within the 3' end of the NS5B coding region of the HCV genome, has been shown essential for efficient viral replication. Its sequence and structural features determine its involvement in functional interactions with viral RNA-dependent RNA polymerase and distant RNA domains of the viral genome. This work reports the use of an in vitro selection strategy to select aptamer RNA molecules against the complete HCV-CRE. After six selection cycles, five potential target sites were identified within this domain. Inhibition assays using a sample of representative aptamers showed that the selected RNAs significantly inhibit the replication (>80%) of a subgenomic HCV replicon in Huh-7 cell cultures. These results highlight the potential of aptamer RNA molecules as therapeutic antiviral agents.
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Received: 5 March 2012; in revised form: 19 April 2012 / Accepted: 10 May 2012 / Published: 18 May 2012
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Abstract: The use of nucleic acid derived aptamers has rapidly expanded since the introduction of SELEX in 1990. Nucleic acid aptamers have demonstrated their ability to target a broad range of molecules in ways that rival antibodies, but advances have been very uneven for different biochemical classes of targets, and clinical applications have been slow to emerge. What sets different aptamers apart from each other and from rivaling molecular recognition platforms, specifically proteins? What advantages do aptamers as a reagent class offer, and how do the chemical properties and selection procedures of aptamers influence their function? Do the building blocks of nucleic acid aptamers dictate inherent limitations in the nature of molecular targets, and do existing aptamers give us insight in how these challenges might be overcome? This review is written as an introduction for potential endusers of aptamer technology who are evaluating the advantages of aptamers as a versatile, affordable, yet highly expandable platform to target a broad range of biological processes or interactions.
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Received: 16 February 2013; in revised form: 9 March 2013 / Accepted: 11 March 2013 / Published: 19 March 2013
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Abstract: The potential to emulate or enhance antibodies with nucleic acid aptamers while lowering costs has prompted development of new aptamer-protein, siRNA, drug, and nanoparticle conjugates. Specific focal points of this review discuss DNA aptamers covalently bound at their 3' ends to various proteins for enhanced stability and greater pharmacokinetic lifetimes in vivo. The proteins can include Fc tails of IgG for opsonization, and the first component of complement (C1q) to trigger complement-mediated lysis of antibiotic-resistant Gram negative bacteria, cancer cells and possibly some parasites during vulnerable stages. In addition, the 3' protein adduct may be a biotoxin, enzyme, or may simply be human serum albumin (HSA) or a drug known to bind HSA, thereby retarding kidney and other organ clearance and inhibiting serum exonucleases. In this review, the author summarizes existing therapeutic aptamer conjugate categories and describes his patented concept for PCR-based amplification of double-stranded aptamers followed by covalent attachment of proteins or other agents to the chemically vulnerable overhanging 3' adenine added by Taq polymerase. PCR amplification of aptamers could dramatically lower the current $2,000/gram cost of parallel chemical oligonucleotide synthesis, thereby enabling mass production of aptamer-3'-protein or drug conjugates to better compete against expensive humanized monoclonal antibodies.
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Planned Papers
The below list represents only planned manuscripts. Some of these
manuscripts have not been received by the Editorial Office yet. Papers
submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: Coupling Aptamers to short Interfering RNAs as Therapeutics
Authors: Vittorio de Franciscis and Laura Cerchia
Affiliation: Istituto per l’Endocrinologia e l’Oncologia Sperimentale del CNR ‘‘G. Salvatore’’, Via S. Pansini 5, 80131 Naples, Italy;
E-Mail: defranci@unina.it (V.d.F.)
Abstract: RNA-based approaches are among the most promising strategies aimed at developing safer and more effective therapeutics. RNA therapeutics include small non-coding miRNAs, small interfering RNA, RNA aptamers and more recently small activating RNAs. However, major barriers exist to the use of RNAs as therapeutics as for example: resistance to nucleases present in biological fluids, chemical stability, need of specific cell targeted delivery and easy entry in the cell. Such issues have been addressed by several recent reports that show the possibility to introduce chemical modifications in small RNAs to stabilize the molecular conformation and increase of several folds integrity still preserving their functional activity. Further, several aptamers have been developed as excellent candidates for the specific recognition of cell surface targets. In the recent few years by taking advantage of recent advances in small RNA field molecular bioconjugates have been designed that permit specific targeting and may act as cargoes for cell internalization of small RNAs acting on gene expression that will be discussed in this Review.
Last update: 23 November 2012
