The clinical potential of optogenetic interrogation of pathogenesis

Abstract

Background Opsin‐based optogenetics has emerged as a powerful biomedical tool using light to control protein conformation. Such capacity has been initially demonstrated to control ion flow across the cell membrane, enabling precise control of action potential in excitable cells such as neurons or muscle cells. Further advancement in optogenetics incorporates a greater variety of photoactivatable proteins and results in flexible control of biological processes, such as gene expression and signal transduction, with commonly employed light sources such as LEDs or lasers in optical microscopy. Blessed by the precise genetic targeting specificity and superior spatiotemporal resolution, optogenetics offers new biological insights into physiological and pathological mechanisms underlying health and diseases. Recently, its clinical potential has started to be capitalized, particularly for blindness treatment, due to the convenient light delivery into the eye. Aims and methods This work summarizes the progress of current clinical trials and provides a brief overview of basic structures and photophysics of commonly used photoactivable proteins. We highlight recent achievements such as optogenetic control of the chimeric antigen receptor, CRISPR‐Cas system, gene expression, and organelle dynamics. We discuss conceptual innovation and technical challenges faced by current optogenetic research. Conclusion In doing so, we provide a framework that showcases ever‐growing applications of optogenetics in biomedical research and may inform novel precise medicine strategies based on this enabling technology.

Split‐Cas9‐based targeted gene editing and nanobody‐mediated proteolysis‐targeting chimeras optogenetically coordinated regulation of Survivin to control the fate of cancer cells

“… 51 The process involves introducing the components of the photocontrol system or cells containing the therapeutic gene into the human body and using light to induce the degradation of the target gene at the transcriptional and protein levels, thereby achieving a therapeutic effect. 52 , 53 In this study, we combined the paProtacL and paCas9 systems (Figure 8 ). We found that they were more effective in degrading Survivin levels than alone and that the combination promoted apoptosis and inhibited migration and proliferation of bladder cancer cells in vitro.…”