Construction of a T _m-value prediction model and molecular dynamics study of AmNA-containing gapmer antisense oligonucleotide.

ABSTRACT: 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 (T _m ) values. The T _m is a critical parameter for designing effective gapmer ASOs to ensure proper functioning. However, p

SUBMITTER: Kuroda M 

PROVIDER: S-EPMC11339022 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature