biostudies-literatureUnknown35(3)Kuroda MNational Institute of Biomedical Innovation Health and NutritionRNase H-dependent antisense oligonucleotides (gapmer ASOs) represent a class of nucleic acid therapeutics that bind to target RNA to facilitate RNase H-mediated RNA cleavage, thereby regulating the expression of disease-associated proteins. Integrating artificial nucleic acids into gapmer ASOs enhances their therapeutic efficacy. Among these, amido-bridged nucleic acid (AmNA) stands out for its potential to confer high affinity and stability to ASOs. However, a significant challenge in the design of gapmer ASOs incorporating artificial nucleic acids, such as AmNA, is the accurate prediction of their melting temperature (<i>T</i> _<i>m</i> ) values. The <i>T</i> _<i>m</i> is a critical parameter for designing effective gapmer ASOs to ensure proper functioning. However, pMolecular therapy. Nucleic acids102272https://www.ebi.ac.uk/biostudies/studies/S-EPMC11339022biostudies-literatureConstruction of a <i>T</i> _m-value prediction model and molecular dynamics study of AmNA-containing gapmer antisense oligonucleotide.PMC11339022Hirose MNagao COda MKuroda MMizuguchi KKasahara YYamaguma HfalseConstruction of a <i>T</i> _m-value prediction model and molecular dynamics study of AmNA-containing gapmer antisense oligonucleotide.RNase H-dependent antisense oligonucleotides (gapmer ASOs) represent a class of nucleic acid therapeutics that bind to target RNA to facilitate RNase H-mediated RNA cleavage, thereby regulating the expression of disease-associated proteins. Integrating artificial nucleic acids into gapmer ASOs enhances their therapeutic efficacy. Among these, amido-bridged nucleic acid (AmNA) stands out for its potential to confer high affinity and stability to ASOs. However, a significant challenge in the design of gapmer ASOs incorporating artificial nucleic acids, such as AmNA, is the accurate prediction of their melting temperature (<i>T</i> _<i>m</i> ) values. The <i>T</i> _<i>m</i> is a critical parameter for designing effective gapmer ASOs to ensure proper functioning. However, p2024-01-01T00:00:00Z2024 Sep2025-04-04T07:55:48.701Z2025-04-04T07:55:48.701ZS-EPMC113390223917617310.1016/j.omtn.2024.102272