Aptamers come of age - At last

Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
Nature Reviews Microbiology (Impact Factor: 23.57). 09/2006; 4(8):588-96. DOI: 10.1038/nrmicro1458
Source: PubMed


Nucleic-acid aptamers have the molecular recognition properties of antibodies, and can be isolated robotically for high-throughput applications in diagnostics, research and therapeutics. Unlike antibodies, however, they can be chemically derivatized easily to extend their lifetimes in biological fluids and their bioavailability in animals. The first aptamer-based clinical drugs have recently entered service. Meanwhile, active research programmes have identified a wide range of anti-viral aptamers that could form the basis for future therapeutics.

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    • "Selection of aptamers is an in vitro process (SELEX) and once selected, they can be synthesized in a controlled fashion with high purity and reproducibility. Additionally , aptamers are chemically more stable than antibodies, retaining most of their functionality even after multiple regeneration steps (Bunka and Stockley, 2006; Jolly et al., 2014; O'Sullivan, 2002; Song et al., 2008). As oligonucleotides can be easily modified with different reactive chemical groups, their immobilization on surfaces can be easily controlled, unlike antibodies . "
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    ABSTRACT: Two novel sandwich-based immunoassays for prostate cancer (PCa) diagnosis are reported, in which the primary antibody for capture is replaced by a DNA aptamer. The assays, which can be performed in parallel, were developed in a microfluidic device and tested for the detection of free Prostate Specific Antigen (fPSA). A secondary antibody (Aptamer-Antibody Assay) or a lectin (Aptamer-Lectin Assay) is used to quantify, by chemiluminescence, both the amount of fPSA and its glycosylation levels. The use of aptamers enables a more reliable, selective and controlled sensing of the analyte. The dual approach provides sensitive detection of fPSA along with selective fPSA glycoprofiling, which is of significant importance in the diagnosis and prognosis of PCa, as tumor progression is associated with changes in fPSA glycosylation. With these approaches, we can potentially detect 0.5ng/mL of fPSA and 3ng/mL of glycosylated fPSA using Sambucus nigra (SNA) lectin, both within the relevant clinical range. The approach can be applied to a wide range of biomarkers, thus providing a good alternative to standard antibody-based immunoassays with significant impact in medical diagnosis and prognosis.
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    • "In this respect, RNA and to a lesser extent DNA scaffolds offer clear advantages over protein scaffolds. Not only, since over time a vast library of aptamers has been created (Bunka and Stockley, 2006), but more importantly since RNA scaffolds exhibit the required structural flexibility and can be (more) rationally designed (Delebecque et al., 2012). These features are considered essential to further advance these emerging applications. "
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    ABSTRACT: Synthetic biology, in close concert with systems biology, is revolutionizing the field of metabolic engineering by providing novel tools and technologies to rationally, in a standardized way, reroute metabolism with a view to optimally converting renewable resources into a broad range of bio-products, bio-materials and bio-energy. Increasingly, these novel synthetic biology tools are exploiting the extensive programmable nature of RNA, vis-à-vis DNA- and protein-based devices, to rationally design standardized, composable, and orthogonal parts, which can be scaled and tuned promptly and at will. This review gives an extensive overview of the recently developed parts and tools for i) modulating gene expression ii) building genetic circuits iii) detecting molecules, iv) reporting cellular processes and v) building RNA nanostructures. These parts and tools are becoming necessary armamentarium for contemporary metabolic engineering. Furthermore, the design criteria, technological challenges, and recent metabolic engineering success stories of the use of RNA devices are highlighted. Finally, the future trends in transforming metabolism through RNA engineering are critically evaluated and summarized.
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    • "Aptamers are artificial oligonucleotides (DNA or RNA) selected in vitro that bind a broad range of biomedically relevant targets with high affinity and specificity. These molecules are useful in biotechnological and therapeutic applications and offer advantages over antibodies due to their facile chemical syntheses and engineering and low or no immunogenicity [1] [2]. Nucleic acid aptamers act as inhibitors with great promise, in particular as targeting ligands for treatments or diagnoses of cancer, HIV and other diseases [3]. "
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    ABSTRACT: We describe the facile syntheses of new modified oligonucleotides based on d(TG3AG) that form bimolecular G-quadruplexes and possess a HEG loop as an inversion of polarity site 3'-3' or 5'-5' and aromatic residues conjugated to the 5'-end through phosphodiester bonds. The conjugated hairpin G-quadruplexes exhibited parallel orientation, high thermal stability, elevated resistance in human serum and high or moderate anti-HIV-1 activity with low cytotoxicity. Further, these molecules showed significant binding to HIV envelope glycoproteins gp120, gp41 and HSA, as revealed by SPR assays. As a result, these conjugated hairpins represent the first active anti-HIV-1 bimolecular G-quadruplexes based on the d(TG3AG) sequence. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
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