A KAIST research team led by Professor Won Do Heo (Department of Biological Sciences) has developed an optogenetic platform, RELISR (REversible LIght-induced Store and Release), that enables precise spatiotemporal control over the storage and release of proteins and mRNAs in living cells and animals.

Traditional optogenetic condensate systems have been limited by their reliance on non-specific multivalent interactions, which can lead to unintended sequestration or release of endogenous molecules. RELISR overcomes these limitations by employing highly specific protein–protein (nanobody–antigen) and protein–RNA (MCP–MS2) interactions, enabling the selective and reversible compartmentalization of target proteins or mRNAs within engineered, membrane-less condensates.

In the dark, RELISR stably sequesters target molecules within condensates, physically isolating them from the cellular environment. Upon blue light stimulation, the condensates rapidly dissolve, releasing the stored proteins or mRNAs, which immediately regain their cellular functions or translational competency. This allows for reversible and rapid modulation of molecular activities in response to optical cues.
The research team demonstrated that RELISR enables temporal and spatial regulation of protein activity and mRNA translation in various cell types, including cultured neurons and mouse liver tissue. Comparative studies showed that RELISR provides more robust and reversible control of translation than previous systems based on spatial translocation.While previous optogenetic systems such as LARIAT (Lee et al., Nature Methods, 2014) and mRNA-LARIAT (Kim et al., Nat. Cell Biol., 2019) enabled the selective sequestration of proteins or mRNAs into membrane-less condensates in response to light, they were primarily limited to the trapping phase. The RELISR platform introduced in this study establishes a new paradigm by enabling both the targeted storage of proteins and mRNAs and their rapid, light-triggered release. This approach allows researchers to not only confine molecular function on demand, but also to restore activity with precise temporal control.

Professor Heo stated, “RELISR is a versatile optogenetic tool that enables the precise control of protein and mRNA function at defined times and locations in living systems. We anticipate this platform will be broadly applicable for studies of cell signaling, neural circuits, and therapeutic development. Furthermore, the combination of RELISR with genome editing or tissue-targeted delivery could further expand its utility for molecular medicine.”

This research was conducted by first author Dr. Chaeyeon Lee, under the supervision of Professor Heo, with contributions from Dr. Daseuli Yu (co-corresponding author) and Professor YongKeun Park (co-corresponding author, Department of Physics), whose group performed quantitative imaging analyses of biophysical changes induced by RELISR in cells.

The findings were published in Nature Communications (July 7, 2025; DOI: 10.1038/s41467-025-61322-y). This work was supported by the Samsung Future Technology Foundation and the National Research Foundation of Korea.