Curated Optogenetic Publication Database

Abstract: CRISPR-based base editors (BEs) are powerful tools for precise nucleotide substitution in a wide range of organisms, but spatiotemporal control of base editing remains a daunting challenge. Herein, we develop a photoactivatable base editor (Mag-ABE) for spatiotemporally controlled genome editing in vivo for the first time. The base editing activity of Mag-ABE can be activated by blue light for spatiotemporal regulation of both EGFP reporter gene and various endogenous genes editing. Meanwhile, the Mag-ABE prefers to edit A4 and A5 positions rather than to edit A6 position, showing the potential to decrease bystander editing of traditional adenine base editors. After integration with upconversion nanoparticles as a light transducer, the Mag-ABE is further applied for near-infrared (NIR) light-activated base editing of liver in transgenic reporter mice successfully. This study opens a promising way to improve the operability, safety, and precision of base editing.

Abstract: Bcl-2-associated X protein (BAX) plays a vital role in maintaining tissue homeostasis and participates in the pathogenesis of various diseases. Poor spatiotemporal control remains a challenge in direct pharmacological modulation and genetic perturbation of BAX’s activity. Herein, we developed a near-infrared (NIR) light-inducible BAX (NiBAX) system that enabled remote and spatiotemporal control of BAX-mediated apoptosis. The NiBAX was constructed by integration of two independent modules: blue light-responsive optogenetics BAX plasmids for regulating migration of BAX to mitochondria and upconversion nanoparticles-encapsulated flexible implant for converting tissue-penetrative NIR light into blue light. This NiBAX could readily induce robust BAX-based cellular apoptosis in vitro, and elicit effective apoptosis-mediated oncotherapy in vivo under NIR light. Collectively, the upconversion optogenetic NiBAX system provides an advanced tool for BAX-related cellular behavior control.