Antisense oligonucleotide-based switches for conditional translation of synthetic mRNA.

ABSTRACT: Synthetic messenger RNA (mRNA) therapeutics requires precise control over their translation to minimize off-target effects. We introduce an antisense oligonucleotide (ASO)-based switch concept that regulates synthetic mRNA translation based on the presence of a complementary trigger RNA (trigRNA). We evaluate variations in ASO hybridization length, position, and chemistry in rabbit reticulocyte lysate (RRL) assays and HEK293T cells. In addition, we explore multiple ASO delivery strategies, including lipid and dendrimer conjugation. Our experiments demonstrate that increased ASO hybridization length and concentration enhance suppression while also improving the OFF/ON dynamic range in the presence of trigRNA. Cell experiments revealed that cholesterol or dendrimer-conjugated phosphorodiamid

SUBMITTER: Combes F 

PROVIDER: S-EPMC12589868 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature