Curated Optogenetic Publication Database

Search precisely and efficiently by using the advantage of the hand-assigned publication tags that allow you to search for papers involving a specific trait, e.g. a particular optogenetic switch or a host organism.

Qr: author:"Giang N T Le"
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1.

An ultralow-background far-red light-responsive optogenetic tool based on an engineered biliverdin-binding domain.

blue red FenixS/Ash1 iLID iLight MagRed nanoReD CHO-K1 HEK293T HeLa in vitro Transgene expression Organelle manipulation Benchmarking
Nat Methods, 11 Sep 2026 DOI: 10.1038/s41592-026-03223-6 Link to full text
Abstract: The robustness and broad applicability of an optogenetic tool depends heavily on the properties of the underlying photoreceptor protein and its cognate binding partner-the light-responsive 'core'. Current red light optogenetic systems for mammalian cells rely on phytochrome-based photoreceptors: large (70-kDa) proteins that act as dimers, enforcing dimerization on attached proteins. Naturally occurring or engineered binding partners can function effectively, but large size, complex interaction, background binding, weak affinity and modest dynamic range remain limiting. Here we developed a small (17-kDa) monomeric biliverdin-binding photoreceptor, FenixS, and a highly selective, high-affinity binder, Ash1 (6 kDa) using structure-based design and directed evolution. Negligible OFF-state binding and a >1,200-fold increase in binding affinity upon 700-nm illumination yield a high-performance, ultralow background core for diverse applications. A FenixS-Ash1-based optogenetic tool for red light activation of transcription in mammalian cells performs robustly without biliverdin supplementation, with head-to-head comparisons confirming its control of gene expression versus established tools.
2.

Red-Light-Only Control of Protein-Protein Interactions Using a Cyanobacteriochrome (UNICYCL).

red UNICYCL CHO-K1 in vitro Transgene expression Benchmarking
ACS Cent Sci, 20 Jan 2026 DOI: 10.1021/acscentsci.5c01848 Link to full text
Abstract: Most optogenetic tools are controlled by blue light. Red-light-responsive tools enable multiwavelength applications and allow greater biological tissue penetration with reduced toxicity. Current red-light tools are primarily based on phytochromes, large dimeric proteins with a structurally complex mode of interaction with their binding partners. Here we introduce a small red-light-only responsive system composed of a BNp-Red-1.2 (6 kDa) that binds to a cyanobacteriochrome (CBCR) GAF domain NpF2164g6 (17 kDa) with a Kd ≈ 1-5 μM to form a 1:1 complex in the dark. Red light causes dissociation of the complex by causing a > 25-fold decrease in binding affinity. The CBCR GAF domain reverts to the dark state with a half-life of ∼ 1 min and the complex reforms. Structural analysis using NMR measurements combined with molecular docking and dynamics simulations shows that the binder interacts with the GAF domain and senses isomerization of the bilin chromophore at a site that overlaps the critical tongue domain of phytochromes. This system provides a small, simple red-light-only optogenetic tool that can operate to control protein-protein interactions in vitro and in living cells.
3.

Optimized Phage Display-Based Selection for the Development of Heterodimerizing Optogenetic Tools.

red FenixS/Ash1 E. coli
ASC Synth Biol, 8 May 2025 DOI: 10.1021/acssynbio.5c00167 Link to full text
Abstract: Multiple display techniques, including phage display, mRNA display, and ribosome display, have been used to expand the optogenetic toolbox beyond what nature provides. These techniques are most often applied to the development of binding partners that selectively recognize different conformational states of photoswitchable proteins. However, for some targets, in particular the spectrally diverse cyanobacteriochrome (CBCR) GAF domain family, the subtle differences between conformational states pose a significant challenge to discovering highly selective binders. We present an optimized phage display-based protocol designed to effectively capture these subtle changes. This optimized protocol applies high selection pressure by changing the elution method and tightening negative selection, leading to the enrichment of selective binders. Through multiple selection campaigns, we demonstrate the utility of this protocol for identifying highly selective binders.
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