An RNA-based switch that adjusts gene and mRNA therapies in response to cellular stress

Engineered RNA rheostats can modulate therapeutic protein expression in response to endoplasmic reticulum stress.

• Short RNA elements from XBP1 mRNA can sense ER stress and regulate protein expression.
• Under stress conditions, these elements induce a frameshift that reduces downstream protein output.
• The system effectively controls expression across different delivery methods for DNA and mRNA.
• Activation of the RNA rheostats lowers ER stress markers while maintaining normal expression levels.
• In vivo testing shows regulation of Leronlimab expression using viral vectors.

Simplified