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A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches

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 protei...

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Detalles Bibliográficos
Autor principal: Bruno, John G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816688/
https://www.ncbi.nlm.nih.gov/pubmed/24276022
http://dx.doi.org/10.3390/ph6030340
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author Bruno, John G.
author_facet Bruno, John G.
author_sort Bruno, John G.
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description 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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spelling pubmed-38166882013-11-14 A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches Bruno, John G. Pharmaceuticals (Basel) Review 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. MDPI 2013-03-19 /pmc/articles/PMC3816688/ /pubmed/24276022 http://dx.doi.org/10.3390/ph6030340 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Bruno, John G.
A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches
title A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches
title_full A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches
title_fullStr A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches
title_full_unstemmed A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches
title_short A Review of Therapeutic Aptamer Conjugates with Emphasis on New Approaches
title_sort review of therapeutic aptamer conjugates with emphasis on new approaches
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816688/
https://www.ncbi.nlm.nih.gov/pubmed/24276022
http://dx.doi.org/10.3390/ph6030340
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