Regulatable in vivo gene expression via adaptamers.

Adaptamers, a compact RNA switch, enable precise, reversible control of transgene expression via small-molecule-dependent ADAR-mediated RNA editing in vivo.

• Why it matters: Controlling gene therapy safely and durably requires systems that are easy to translate in vivo, but current methods face challenges like large size and limited duration.
• What they did: Researchers developed adaptamers, less than 120 base pairs long, that couple FDA-approved aptamers with endogenous ADAR to regulate gene expression through a ligand-stabilized RNA structure in multiple cell lines and in mice.
• The result: In mice, adaptamer-controlled FGF21 expression via AAV delivery reversed obesity and hepatic steatosis, demonstrating potential for tunable, safe genetic medicines.