An ultralow-background far-red light-responsive optogenetic tool based on an engineered biliverdin-binding domain.
An engineered biliverdin-binding domain enables an ultralow-background, red-light-responsive optogenetic system with over 1,200-fold activation in mammalian cells.
- Why it matters: Current phytochrome-based optogenetic tools are limited by their large size, complex interactions, and background activity, restricting their effectiveness and application scope.
- What they did: The team designed a small (17-kDa) monomeric photoreceptor, FenixS, and a high-affinity binder, Ash1 (6 kDa), using structure-based design and directed evolution, achieving highly selective, high-affinity binding with minimal OFF-state activity.
- The result: This system enables robust, biliverdin-independent control of gene expression in mammalian cells with ultralow background, facilitating precise red-light activation for diverse biological applications.