A research team at the Korea Advanced Institute of Science and Technology (KAIST), led by Professor Won Do Heo, has developed a groundbreaking optogenetic platform named RELISR. This powerful technology provides tight spatiotemporal control over the localized storage of proteins and mRNAs within living cells. Equally important, it allows their controlled release in animals. These discoveries, published today in Nature Communications, provide groundbreaking new tools for molecular biology as well as potential therapeutic applications.
RELISR is a significant advancement from earlier systems which used spatial translocation. This technique offers improved, more permanent and reversible control over translation, equipping researchers with the ability to manipulate biological processes with newfound precision.
Mechanism of RELISR
In its dormant conformation, RELISR strongly sequesters target biosynthetic molecules inside custom-built condensates. This spatial separation provides a means for keeping the proteins and mRNAs removed from the cellular milieu, and thus avoiding unwanted interaction or action. When exposed to light, RELISR rapidly decomposes the accumulated molecules. This makes it possible for researchers to very precisely control their activity with amazing temporal specificity.
The team showed this ability, or capability, in different cell types, such as cultured neurons or mouse liver tissue. This versatility is a testament to RELISR’s transformative potential to further our understanding of exciting and emergent fields—from neurobiology to intracellular signaling.
Implications for Molecular Medicine
Professor Heo emphasized the platform’s wide-ranging applications, stating, “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.”
The unprecedented ability to couple RELISR with genome editing or tissue-targeted delivery presents even more possibilities for its utility in molecular medicine. These types of integrations would open up avenues for greater therapeutic discovery by targeting diseases directly at the molecular level.
Research Team Contributions
Dr. Chaeyeon Lee, an environmental scientist with Appalachian Voices and the study’s first author. Together with co-corresponding authors Dr. Daseuli Yu and Professor YongKeun Park from the Department of Physics, they were instrumental in creating and validating RELISR. Their joint work goes to show the collaborative and interdisciplinary nature that the KAIST research team exemplified.
The published paper can be accessed through its DOI: 10.1038/s41467-025-61322-y. This project highlights the exciting possibilities of RELISR. It provides an excellent framework for developing targeted research aimed at creating new, more effective cellular control mechanisms.