Cycloalkane Incorporation Into the 2',4'-Bridge of Locked Nucleic Acid: Enhancing Nuclease Stability, Reducing Phosphorothioate Modifications, and Lowering Hepatotoxicity in Antisense Oligonucleotides.

ABSTRACT: 2'-O,4'-C-Methylene-bridged nucleic acid (2',4'-BNA), also known as locked nucleic acid (LNA), is widely used to modify antisense oligonucleotides (ASOs) because it significantly enhances their ability to form duplexes with target RNAs, thereby boosting ASO activity. However, 2',4'-BNA/LNA exhibits only moderate nuclease stability, necessitating additional modifications, such as phosphorothioate (PS) linkages. Our previous studies demonstrated that oligonucleotides modified with 2'-O,4'-C-spirocyclopropylene-bridged nucleic acid (scpBNA) retain duplex-forming abilities similar to those of 2',4'-BNA/LNA, while showing significantly improved nuclease stability. In the present study, we introduce 2'-O,4'-C-spirocyclopentylene-bridged nucleic acid (scp

SUBMITTER: Yamaguchi T 

PROVIDER: S-EPMC12569656 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature