Chemical evolution of ASO-like DNAzymes for effective and extended gene silencing in cells.

ABSTRACT: Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) therapeutics highlight the power of oligonucleotides in silencing disease-causing messenger RNAs (mRNAs). Another promising class of gene-silencing oligonucleotides is RNA-cleaving nucleic acid enzymes, which offer the potential for allele-specific RNA inhibition with greater precision than ASOs and siRNAs. Herein, we chemically evolved the nucleolytic DNA enzyme (DNAzyme) 10-23, by incorporating the modifications that are essential to the success of ASO drugs, including 2'-fluoro, 2'-O-methyl, and 2'-O-methoxyethyl RNA analogues, and backbone phosphorothioate, to enhance catalytic efficiency by promoting RNA substrate binding and preventing dimerization of 10-23. These ASO-like DNAzymes cleaved structured RNA targets in l

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11879453 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature