Optogenetic methods in drug screening: technologies and applications

- All-optical screening platforms emerged in recent years.
- Incorporation of optogenetic methods improved throughput and reduced cost.
- Unique pitfalls exist that can be addressed with adequate controls.
- The all-optical approach is versatile and only the tip of the iceberg has been touched.

The optogenetic revolution enabled spatially-precise and temporally-precise control over protein function, signaling pathway activation, and animal behavior with tremendous success in the dissection of signaling networks and neural circuits. Very recently, optogenetic methods have been paired with optical reporters in novel drug screening platforms. In these all-optical platforms, light remotely activated ion channels and kinases thereby obviating the use of electrophysiology or reagents. Consequences were remarkable operational simplicity, throughput, and cost-effectiveness that culminated in the identification of new drug candidates. These blueprints for all-optical assays also revealed potential pitfalls and inspire all-optical variants of other screens, such as those that aim at better understanding dynamic drug action or orphan protein function.

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