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      Artificially Expanded Genetic Information Systems for New Aptamer Technologies

      review-article
      Author(s): 1 , 2 , * , 1 , 2
      Publication date (Electronic):
      Journal: Biomedicines
      Publisher: MDPI
      Keywords: expanded alphabet, AEGIS, aptamers, in vitro selection

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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 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”.

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          Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase.

          L Gold, C Tuerk (1990)
          High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species. Multiple rounds exponentially enrich the population for the highest affinity species that can be clonally isolated and characterized. In particular one eight-base region of an RNA that interacts with the T4 DNA polymerase was chosen and randomized. Two different sequences were selected by this procedure from the calculated pool of 65,536 species. One is the wild-type sequence found in the bacteriophage mRNA; one is varied from wild type at four positions. The binding constants of these two RNA's to T4 DNA polymerase are equivalent. These protocols with minimal modification can yield high-affinity ligands for any protein that binds nucleic acids as part of its function; high-affinity ligands could conceivably be developed for any target molecule.
          Article 0 comments Cited 959 times – based on 0 reviews     Review now
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            Aptamers as targeted therapeutics: current potential and challenges

            Jiehua Zhou, John M. Rossi (2016)
            Nucleic acid aptamers offer several advantages over traditional antibodies, but their clinical translation has been delayed by several factors, including insufficient potency, lack of safety data and high production costs. Here, Zhou and Rossi provide an overview of aptamer generation, focusing on recent technological advances and clinical development, as well as challenges and lessons learned.
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              Aptamers: an emerging class of molecules that rival antibodies in diagnostics.

              S D Jayasena (1999)
              Antibodies, the most popular class of molecules providing molecular recognition needs for a wide range of applications, have been around for more than three decades. As a result, antibodies have made substantial contributions toward the advancement of diagnostic assays and have become indispensable in most diagnostic tests that are used routinely in clinics today. The development of the systematic evolution of ligands by exponential enrichment (SELEX) process, however, made possible the isolation of oligonucleotide sequences with the capacity to recognize virtually any class of target molecules with high affinity and specificity. These oligonucleotide sequences, referred to as "aptamers", are beginning to emerge as a class of molecules that rival antibodies in both therapeutic and diagnostic applications. Aptamers are different from antibodies, yet they mimic properties of antibodies in a variety of diagnostic formats. The demand for diagnostic assays to assist in the management of existing and emerging diseases is increasing, and aptamers could potentially fulfill molecular recognition needs in those assays. Compared with the bellwether antibody technology, aptamer research is still in its infancy, but it is progressing at a fast pace. The potential of aptamers may be realized in the near future in the form of aptamer-based diagnostic products in the market. In such products, aptamers may play a key role either in conjunction with, or in place of, antibodies. It is also likely that existing diagnostic formats may change according to the need to better harness the unique properties of aptamers.
              Article 0 comments Cited 317 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomedicines
                Journal ID (iso-abbrev): Biomedicines
                Journal ID (publisher-id): biomedicines
                Title: Biomedicines
                Publisher: MDPI
                ISSN (Electronic): 2227-9059
                Publication date (Electronic): 09 May 2018
                Publication date Collection: June 2018
                Volume: 6
                Issue: 2
                Electronic Location Identifier: 53
                Affiliations
                [1 ]Foundation for Applied Molecular Evolution, Alachua, FL 32615, USA; sbenner@ 123456ffame.org
                [2 ]Firebird Biomolecular Sciences, LLC, Alachua, FL 32615, USA
                Author notes
                [* ]Correspondence: ebiondi@ 123456ffame.org ; Tel.: +1-386-418-8085
                Article
                Publisher ID: biomedicines-06-00053
                DOI: 10.3390/biomedicines6020053
                PMC ID: 6027400
                PubMed ID: 29747381
                SO-VID: 80b39961-341f-4715-8a59-e1cd8a4267cf
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 10 April 2018
                Date accepted : 06 May 2018
                Categories
                Subject: Review

                Keywords: expanded alphabet,aegis,aptamers,in vitro selection
                Data availability:
                Keywords: expanded alphabet, aegis, aptamers, in vitro selection

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