Cell-Specific Aptamers as Emerging Therapeutics (original) (raw)
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Advances and Perspectives in Cell-Specific Aptamers
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Nucleic acid aptamers, generated by an in vitro selection procedure named SELEX (Systematic Evolution of Ligands by EXponential enrichment), have been popularly used in various biomedical implementations so far. An adaptation of the conventional SELEX practice to whole living cells was referred to as cell-SELEX, which is very promising in ample sophisticated analytical, therapeutic and diagnostic applications. The current review article would like to provide a survey of contemporary developments in cell-specific aptamers, including methodology, applications and optimization of cell-SELEX.
Aptamers: An in vitro Evolution of Therapeutic and Diagnostic Applications in Medicine
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Aptamers are nucleic acid oligomers with distinct conformational shapes that allow binding targets with high affinity and specificity. Selective Evolution of Ligands by Exponential Enrichment (SELEX); an in vitro selection process to develop aptamers, has been invented in 1990. Despite more than 20 years have passed after its discovery, products of SELEX technology are in use in medicine. In this review we discuss why we need aptamers not only in therapeutic but also in diagnostic applications; and also critical points in SELEX technology. Finally; we present the aptamers in use and some patented aptamers awaiting approval. 'to fit' and the Greek word 'meros' meaning 'particle'. An aptamer is a DNA or RNA oligonucleotide that has
Aptamers and Their Significant Role in Cancer Therapy and Diagnosis
Aptamers are nucleic acid/peptide molecules that can be generated by a sophisticated, well-established technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers can interact with their targets through structural recognition, as in antibodies, though with higher specificity. With this added advantage, they can be made useful for clinical applications such as targeted therapy and diagnosis. In this review, we have discussed the steps involved in SELEX process and modifications executed to attain high affinity nucleic acid aptamers. Moreover, our review also highlights the therapeutic applications of aptamer functionalized nanoparticles and nucleic acids as chemo-therapeutic agents. In addition, we have described the development of “aptasensor” in clinical diagnostic application for detecting cancer cells and the use of aptamers in different routine imaging techniques, such as Positron Emission Tomography/Computed Tomography, Ultrasound, and Magnetic Resonance Imaging
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Aptamers are short, single-stranded oligonucleotides that are isolated through a process termed systematic evolution of ligands by exponential enrichment.
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Nucleic acids play a central role in all domains of life, either as genetic blueprints or as regulators of various biochemical pathways. The chemical makeup of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), generally represented by a sequence of four monomers, also provides precise instructions for folding and higher-order assembly of these biopolymers that, in turn, dictate biological functions. The sequence-based specific 3D structures of nucleic acids led to the development of the directed evolution of oligonucleotides, SELEX (systematic evolution of ligands by exponential enrichment), against a chosen target molecule. Among the variety of functions, selected oligonucleotides named aptamers also allow targeting of cell-specific receptors with antibody-like precision and can deliver functional RNAs without a transfection agent. The advancements in the field of customizable nucleic acid nanoparticles (NANPs) opened avenues for the design of nanoassemblies utilizing aptamers for triggering or blocking cell signaling pathways or using aptamer-receptor combinations to activate therapeutic functionalities. A recent selection of fluorescent aptamers enables real-time tracking of NANP formation and interactions. The aptamers are anticipated to contribute to the future development of technologies, enabling an efficient assembly of functional NANPs in mammalian cells or in vivo. These research topics are *
Cell-targeting aptamers act as intracellular delivery vehicles
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Aptamers are single-stranded nucleic acids or peptides identified from a randomized combinatorial library through specific interaction with the target of interest. Targets can be of any size, from small molecules to whole cells, attesting to the versatility of aptamers for binding a wide range of targets. Aptamers show drug properties that are analogous to antibodies, with high specificity and affinity to their target molecules. Aptamers can penetrate disease-causing microbial and mammalian cells. Generated aptamers that target surface biomarkers act as cell-targeting agents and intracellular delivery vehicles. Within this context, the "cell-internalizing aptamers" are widely investigated via the process of cell uptake with selective binding during in vivo systematic evolution of ligands by exponential enrichment (SELEX) or by cell-internalization SELEX, which targets cell surface antigens to be receptors. These internalizing aptamers are highly preferable for the localiza...
DNA and RNA Aptamers: From Tools for Basic Research Towards Therapeutic Applications
Combinatorial Chemistry & High Throughput Screening, 2006
The systematic evolution of ligands by exponential enrichment (SELEX) is a combinatorial oligonucleotide library-based in vitro selection approach in which DNA or RNA molecules are selected by their ability to bind their targets with high affinity and specificity, comparable to those of antibodies. Nucleic acids with high affinity for their targets have been selected against a wide variety of compounds, from small molecules, such as ATP, to membrane proteins and even whole organisms. Recently, the use of the SELEX technique was extended to isolate oligonucleotide ligands, also known as aptamers, for a wide range of proteins of importance for therapy and diagnostics, such as growth factors and cell surface antigens. The number of aptamers generated as inhibitors of various target proteins has increased following automatization of the SELEX process. Their diagnostic and therapeutic efficacy can be enhanced by introducing chemical modifications into the oligonucleotides to provide resistance against enzymatic degradation in body fluids. Several aptamers are currently being tested in preclinical and clinical trials, and aptamers are in the process of becoming a new class of therapeutic agents. Recently, the anti-VEGF aptamer pegaptanib received FDA approval for treatment of human ocular vascular disease.
Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries. Abbreviations: SELEX, Systematic Evolution of Ligands by EXponential enrichment; US FDA, United States Food and Drug Administration; AMD, Age-related macular degeneration; VEGF, Vascular endothelial growth factor protein, 2 0-NH 2 , 2 0-Amino; 2 0-OH, 2 0-Hydroxyl; K d , Equilibrium dissociation constant; 2 0-OMe, 2 0-O-Methyl; Bfgf, Basic fibroblast growth factor; 2 0-F, 2 0-Fluoro; PSMA, Prostate specific membrane antigen; IFN-g, Interferon-gamma; KGF, Keratinocyte growth factor; 4 0-S, 4 0-Thio; 2 0-FANA, 2 0-Fluroarabino nucleic acid; HNA, 1,5-Anhydro hexitol nucleic acid; TAR, transactivation responsive element; TNA, Threose nucleic acid; LNA, Locked nucleic acid; SOMAmers, Slow Off-rate Modified Aptamers KEYWORDS Aptamers; chemical antibodies; chemicallymodified aptamers; in vitro selection; modified nucleotides; nucleic acid ligands; SELEX thesis. Generally, a web-based secondary structure prediction algorithm (e.g. mfold, 12 RNAfold 13) is used as a tool to assist with the positioning of chemically-modified nucleotides and to truncate the overall size of the selected aptamers during chemical synthesis. Such chemically-fabricated
Aptamers: multifunctional molecules for biomedical research
Journal of Molecular Medicine, 2013
Aptamers are single-stranded oligonucleotides that fold into well-defined three-dimensional shapes, allowing them to bind their targets with high affinity and specificity. They can be generated through an in vitro process called "Systemic Evolution of Ligands by Exponential Enrichment" and applied for specific detection, inhibition, and characterization of various targets like small organic and inorganic molecules, proteins, and whole cells. Aptamers have also been called chemical antibodies because of their synthetic origin and their similar modes of action to antibodies. They exhibit significant advantages over antibodies in terms of their small size, synthetic accessibility, and ability to be chemically modified and thus endowed with new properties. The first generation of aptamer drug "Macugen" was available for public use within 25 years of the discovery of aptamers. With others in the pipeline for clinical trials, this emerging field of medical biotechnology is raising significant interest. However, aptamers pose different problems for their development than for antibodies that need to be addressed to achieve practical applications. It is likely that current developments in aptamer engineering will be the basis for the evolution of improved future bioanalytical and biomedical applications. The present review discusses the development of aptamers for therapeutics, drug delivery, target validation and imaging, and reviews some of the challenges to fully realizing the promise of aptamers in biomedical applications.