Open AccessRefining LNA safety profile by controlling phosphorothioate stereochemistry
Author(s) -
Erik Daa Funder,
Nanna Albæk,
Annie Moisan,
Sabine Sewing,
Troels Koch
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0232603
Subject(s) - oligonucleotide , stereocenter , in vitro , chemistry , computational biology , stereochemistry , pharmacology , biochemistry , biology , gene , catalysis , enantioselective synthesis
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.