Synthesis, Biological Activity, and Molecular Dynamics Simulations of LNA-Charge Neutral Linkages for Enhanced Splice-Switching Antisense Oligonucleotides.

ABSTRACT: Antisense oligonucleotides are promising therapeutic agents for a range of diseases, having found special clinical success for splice-switching genetic conditions such as spinal muscular atrophy and Duchenne muscular dystrophy. However, novel chemistries are still required to discover modifications which improve their druggable properties. For in vitro studies, thermal duplex stability, resistance to enzymatic degradation and gymnotic cellular activity are important, and biodistribution, toxicology and potency must be optimised for clinical progression. We investigate the combination of locked nucleic acids (LNA) and charge neutral backbones in chimeric ASOs containing 2'-O-methyl sugars and phosphorothioate backbones by evaluating their physical and biological properties. Backbones invest

SUBMITTER: Kennett A 

PROVIDER: S-EPMC12603973 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature