Cargando…
Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds
Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920040/ https://www.ncbi.nlm.nih.gov/pubmed/29731743 http://dx.doi.org/10.3389/fmicb.2018.00750 |
_version_ | 1783317752144986112 |
---|---|
author | Nan, Yuchen Zhang, Yan-Jin |
author_facet | Nan, Yuchen Zhang, Yan-Jin |
author_sort | Nan, Yuchen |
collection | PubMed |
description | Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD) has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided. |
format | Online Article Text |
id | pubmed-5920040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59200402018-05-04 Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds Nan, Yuchen Zhang, Yan-Jin Front Microbiol Microbiology Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD) has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided. Frontiers Media S.A. 2018-04-20 /pmc/articles/PMC5920040/ /pubmed/29731743 http://dx.doi.org/10.3389/fmicb.2018.00750 Text en Copyright © 2018 Nan and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Nan, Yuchen Zhang, Yan-Jin Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds |
title | Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds |
title_full | Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds |
title_fullStr | Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds |
title_full_unstemmed | Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds |
title_short | Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds |
title_sort | antisense phosphorodiamidate morpholino oligomers as novel antiviral compounds |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920040/ https://www.ncbi.nlm.nih.gov/pubmed/29731743 http://dx.doi.org/10.3389/fmicb.2018.00750 |
work_keys_str_mv | AT nanyuchen antisensephosphorodiamidatemorpholinooligomersasnovelantiviralcompounds AT zhangyanjin antisensephosphorodiamidatemorpholinooligomersasnovelantiviralcompounds |