Effect of chemical modification on the exon-skipping activity of heteroduplex oligonucleotides.

ABSTRACT: We applied heteroduplex oligonucleotide (HDO) technology, which uses an oligonucleotide hybridized with a complementary strand, to efficiently deliver locked nucleic acid (LNA)-based splice-switching oligonucleotides (SSOs) to the nucleus. Using an in vitro assay involving cationic lipids, we revealed that HDO technology increased the exon-skipping activity of LNA-based SSOs. To assess the effect of heteroduplex SSOs (HDSSOs) on exon-skipping activity, we designed and evaluated various HDSSOs using a series of complementary oligonucleotides with different sugar chemistries (DNA, RNA, and LNA), linkages (phosphodiester; PO and phosphorothioate; PS linkages), and lengths. HDO with different complementary oligonucleotide designs demonstrated a variety of exon-skipping activities. Next,

SUBMITTER: Shimo T 

PROVIDER: S-EPMC11875208 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature