AUTHOR=Flynn Loren L. , Li Ruohan , Pitout Ianthe L. , Aung-Htut May T. , Larcher Leon M. , Cooper Jack A. L. , Greer Kane L. , Hubbard Alysia , Griffiths Lisa , Bond Charles S. , Wilton Steve D. , Fox Archa H. , Fletcher Sue TITLE=Single Stranded Fully Modified-Phosphorothioate Oligonucleotides can Induce Structured Nuclear Inclusions, Alter Nuclear Protein Localization and Disturb the Transcriptome In Vitro JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.791416 DOI=10.3389/fgene.2022.791416 ISSN=1664-8021 ABSTRACT=
Oligonucleotides and nucleic acid analogues that alter gene expression are now showing therapeutic promise in human disease. Whilst the modification of synthetic nucleic acids to protect against nuclease degradation and to influence drug function is common practice, such modifications may also confer unexpected physicochemical and biological properties. Gapmer mixed-modified and DNA oligonucleotides on a phosphorothioate backbone can bind non-specifically to intracellular proteins to form a variety of toxic inclusions, driven by the phosphorothioate linkages, but also influenced by the oligonucleotide sequence. Recently, the non-antisense or other off-target effects of 2′