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Refining LNA safety profile by controlling phosphorothioate stereochemistry.

ABSTRACT: 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.

SUBMITTER: Funder ED

PROVIDER: S-EPMC7292364 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Refining LNA safety profile by controlling phosphorothioate stereochemistry.

Funder Erik Daa ED Albæk Nanna N Moisan Annie A Sewing Sabine S Koch Troels T

PloS one 20200612 6

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. ...[more]

PMID: 32530964

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