Refining LNA safety profile by controlling phosphorothioate stereochemistry

Drug discovery with phosphorothioate oligonucleotides is an area of intensive research. In this study we have controlled the stereochemistry of the phosphorothioate backbone of LNA oligonucleotides to investigate the differences in safety profile, target mRNA knock down, and cellular uptake in vitro...

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Autores principales: Funder, Erik Daa, Albæk, Nanna, Moisan, Annie, Sewing, Sabine, Koch, Troels
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292364/
https://www.ncbi.nlm.nih.gov/pubmed/32530964
http://dx.doi.org/10.1371/journal.pone.0232603
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author Funder, Erik Daa
Albæk, Nanna
Moisan, Annie
Sewing, Sabine
Koch, Troels
author_facet Funder, Erik Daa
Albæk, Nanna
Moisan, Annie
Sewing, Sabine
Koch, Troels
author_sort Funder, Erik Daa
collection PubMed
description Drug discovery with phosphorothioate oligonucleotides is an area of intensive research. In this study we have controlled the stereochemistry of the phosphorothioate backbone of LNA oligonucleotides to investigate the differences in safety profile, target mRNA knock down, and cellular uptake in vitro. The study reveals that controlling only four stereocenters in an isomeric phosphorothioate mixture can improve the therapeutic index significantly by improving safety without compromising activity.
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spelling pubmed-72923642020-06-18 Refining LNA safety profile by controlling phosphorothioate stereochemistry Funder, Erik Daa Albæk, Nanna Moisan, Annie Sewing, Sabine Koch, Troels PLoS One Research Article Drug discovery with phosphorothioate oligonucleotides is an area of intensive research. In this study we have controlled the stereochemistry of the phosphorothioate backbone of LNA oligonucleotides to investigate the differences in safety profile, target mRNA knock down, and cellular uptake in vitro. The study reveals that controlling only four stereocenters in an isomeric phosphorothioate mixture can improve the therapeutic index significantly by improving safety without compromising activity. Public Library of Science 2020-06-12 /pmc/articles/PMC7292364/ /pubmed/32530964 http://dx.doi.org/10.1371/journal.pone.0232603 Text en © 2020 Funder et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Funder, Erik Daa
Albæk, Nanna
Moisan, Annie
Sewing, Sabine
Koch, Troels
Refining LNA safety profile by controlling phosphorothioate stereochemistry
title Refining LNA safety profile by controlling phosphorothioate stereochemistry
title_full Refining LNA safety profile by controlling phosphorothioate stereochemistry
title_fullStr Refining LNA safety profile by controlling phosphorothioate stereochemistry
title_full_unstemmed Refining LNA safety profile by controlling phosphorothioate stereochemistry
title_short Refining LNA safety profile by controlling phosphorothioate stereochemistry
title_sort refining lna safety profile by controlling phosphorothioate stereochemistry
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292364/
https://www.ncbi.nlm.nih.gov/pubmed/32530964
http://dx.doi.org/10.1371/journal.pone.0232603
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