Chemically inducible antisense oligonucleotides for cell-specific gene silencing.

ABSTRACT: Cell-specific control of the function of antisense oligonucleotides (ASOs) is highly desirable for precise gene therapy while minimizing adverse effects in normal cells. Herein, we report a novel class of chemically inducible ASOs (iASOs) that achieve tumor-cell-selective gene silencing through hydrogen peroxide (H₂O₂)-triggered activation. Through post-synthetic incorporation of phenylboronic acid (BO) caging groups at the backbone positions, we developed iASOs that remain functionally inactive until the H₂O₂-triggered removal of the BO groups caused activation. Using EGFP as a reporter system, we demonstrated that the optimal BO-modified iASO exhibited slight gene silencing activity in normal cells but achieved >80% knockdown of the target mRNA

SUBMITTER: Xun Z 

PROVIDER: S-EPMC12538225 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature