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Molecular Mechanisms of Antisense Oligonucleotides

In 1987, when I became interested in the notion of antisense technology, I returned to my roots in RNA biochemistry and began work to understand how oligonucleotides behave in biological systems. Since 1989, my research has focused primarily on this topic, although I have been involved in most areas...

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Autor principal: Crooke, Stanley T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372764/
https://www.ncbi.nlm.nih.gov/pubmed/28080221
http://dx.doi.org/10.1089/nat.2016.0656
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author Crooke, Stanley T.
author_facet Crooke, Stanley T.
author_sort Crooke, Stanley T.
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description In 1987, when I became interested in the notion of antisense technology, I returned to my roots in RNA biochemistry and began work to understand how oligonucleotides behave in biological systems. Since 1989, my research has focused primarily on this topic, although I have been involved in most areas of research in antisense technology. I believe that the art of excellent science is to frame large important questions that are perhaps not immediately answerable with existing knowledge and methods, and then conceive a long-term (multiyear) research strategy that begins by answering the most pressing answerable questions on the path to the long-term goals. Then, a step-by-step research pathway that will address the strategic questions posed must be implemented, adjusting the plan as new things are learned. This is the approach we have taken at Ionis. Obviously, to create antisense technology, we have had to address a wide array of strategic questions, for example, the medicinal chemistry of oligonucleotides, manufacturing and analytical methods, pharmacokinetics and toxicology, as well as questions about the molecular pharmacology of antisense oligonucleotides (ASOs). Each of these endeavors has consumed nearly three decades of scientific effort, is still very much a work-in-progress, and has resulted in hundreds of publications. As a recipient of the Lifetime Achievement Award 2016 granted by the Oligonucleotide Therapeutic Society, in this note, my goal is to summarize the contributions of my group to the efforts to understand the molecular mechanisms of ASOs.
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spelling pubmed-53727642017-05-03 Molecular Mechanisms of Antisense Oligonucleotides Crooke, Stanley T. Nucleic Acid Ther Issues in Development In 1987, when I became interested in the notion of antisense technology, I returned to my roots in RNA biochemistry and began work to understand how oligonucleotides behave in biological systems. Since 1989, my research has focused primarily on this topic, although I have been involved in most areas of research in antisense technology. I believe that the art of excellent science is to frame large important questions that are perhaps not immediately answerable with existing knowledge and methods, and then conceive a long-term (multiyear) research strategy that begins by answering the most pressing answerable questions on the path to the long-term goals. Then, a step-by-step research pathway that will address the strategic questions posed must be implemented, adjusting the plan as new things are learned. This is the approach we have taken at Ionis. Obviously, to create antisense technology, we have had to address a wide array of strategic questions, for example, the medicinal chemistry of oligonucleotides, manufacturing and analytical methods, pharmacokinetics and toxicology, as well as questions about the molecular pharmacology of antisense oligonucleotides (ASOs). Each of these endeavors has consumed nearly three decades of scientific effort, is still very much a work-in-progress, and has resulted in hundreds of publications. As a recipient of the Lifetime Achievement Award 2016 granted by the Oligonucleotide Therapeutic Society, in this note, my goal is to summarize the contributions of my group to the efforts to understand the molecular mechanisms of ASOs. Mary Ann Liebert, Inc. 2017-04-01 2017-04-01 /pmc/articles/PMC5372764/ /pubmed/28080221 http://dx.doi.org/10.1089/nat.2016.0656 Text en © Stanley T. Crooke, 2017; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Issues in Development
Crooke, Stanley T.
Molecular Mechanisms of Antisense Oligonucleotides
title Molecular Mechanisms of Antisense Oligonucleotides
title_full Molecular Mechanisms of Antisense Oligonucleotides
title_fullStr Molecular Mechanisms of Antisense Oligonucleotides
title_full_unstemmed Molecular Mechanisms of Antisense Oligonucleotides
title_short Molecular Mechanisms of Antisense Oligonucleotides
title_sort molecular mechanisms of antisense oligonucleotides
topic Issues in Development
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372764/
https://www.ncbi.nlm.nih.gov/pubmed/28080221
http://dx.doi.org/10.1089/nat.2016.0656
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