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X-WR-CALNAME:Oligonucleotide Therapeutics Society
X-WR-CALDESC:Oligonucleotide Therapeutics Society
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DTSTART:20260514T084943
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UID:MEC-119a1021b468c9e4ce558c01672f9e4f@oligotherapeutics.org
DTSTART;TZID=UTC:20240829T170000
DTEND;TZID=UTC:20240829T190000
DTSTAMP:20240821T042748Z
CREATED:20240821
LAST-MODIFIED:20240821
PRIORITY:5
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TRANSP:OPAQUE
SUMMARY:Sequence- and Structure-Dependent Cytotoxicity of Phosphorothioate and 2’-O-Methyl Modified Single-Stranded Oligonucleotides
DESCRIPTION:Single-stranded oligonucleotides (SSOs) are a rapidly expanding class of therapeutics. Chemical modifications such as the phosphorothioate (PS) backbone and the 2’-O-methyl (2’-OMe) ribose can improve the stability and pharmacokinetic properties of therapeutic SSOs, but they can also lead to toxicity in vitro and in vivo. In this study, we screened a mini library of 277 PS and 2’-OMe- modified SSOs, with or without mRNA complementarity, for cytotoxic properties in two cancer cell lines. Using circular dichroism, nucleic magnetic resonance, and molecular dynamics simulations, we show that PS- and 2’-OMe -modified SSOs that form stable hairpin structures through Watson–Crick base pairing are more likely to be cytotoxic than those that exist in an extended conformation. Overall, our study demonstrates a structure–cytotoxicity relationship and indicates that the formation of stable hairpins should be a consideration when designing SSOs toward optimal therapeutic profiles.\n
URL:http://oligotherapeutics.org/sequence-and-structure-dependent-cytotoxicity-of-phosphorothioate-and-2-o-methyl-modified-single-stranded-oligonucleotides/
CATEGORIES:Webinar
ATTACH;FMTTYPE=image/webp:https://oligotherapeutics.org/wp-content/uploads/2024/08/08-29-2024.webp
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