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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Detalles Bibliográficos
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
Descripción
Sumario: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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