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KAIST Team Develops Optogenetic Platform for Spatiotemporal Control of Protein and mRNA Storage and Release
<Dr. Chaeyeon Lee, Professor Won Do Heo from Department of Biological Sciences>
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.
< Figure 1. Overview of the Artificial Condensate System (RELISR). The artificial condensate system, RELISR, includes "Protein-RELISR" for storing proteins and "mRNA-RELISR" for storing mRNA. These artificial condensates can be disassembled by blue light irradiation and reassembled in a dark state>
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.
< Figure 2. Cell shape change using the artificial condensate system (RELISR). A target protein, Vav2, which contributes to cell shape, was stored within the artificial condensate and then released after light irradiation. This release activated the target protein Vav2, causing a change in cell shape. It was confirmed that the storage, release, and activation of various proteins were effectively achieved>
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.”
< Figure 3. Expression of a target mRNA using the artificial condensate system (RELISR) in mice. The genetic material for the artificial condensate system, RELISR, was injected into a living mouse. Using this system, a target mRNA was stored within the mouse's liver. Upon light irradiation, the mRNA was released, which induced the translation of a luminescent protein>
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.
2025.07.23 View 322 -
A 10-Month Journey of Tiny Flaps Completed: A Special Family Returns to KAIST Duck Pond
On the morning of June 9, 2025, gentle activity stirred early around the KAIST campus duck pond. It was the day a special family of ducks—and two goslings—were to be released back into the pond after spending a month in a temporary shelter. One by one, the ducklings cautiously emerged from their box, waddling toward the water's edge and scanning their surroundings, followed closely by their mother.
< The landscape manager from the KAIST Facilities Team releases the ducks and goslings. >
The mother duck, once a rescued loner who couldn’t integrate with the flock, returned triumphantly as the head of a new family—caring for both ducklings and goslings. Students and faculty looked on quietly, welcoming them back and reflecting on their remarkable 10-month journey.
The story began in July 2024, as a student filed a report of spotting two ducklings wandering near the pond without a mother. Based on their soft down, flat beaks, and lack of fear around humans, it was presumed they had been abandoned. Professor Won Do Heo of the Department of Biological Sciences—affectionately known as the “Goose Dad”—and the KAIST Facilities Team quickly stepped in to rescue them. After about a month of care, the ducklings were released back into the pond.
< On June 9, the day of the release, KAIST President Kwang-Hyung Lee (left), the former “Goose Dad,” and Professor Won Do Heo (right), the current “Goose Dad,” watched the flock as they freely wobbled about. >
At first, the ducklings seemed to adapt, but they started distancing themselves from the established goose flock. One eventually disappeared, and the remaining duckling was found injured by the pond during winter. Although KAIST typically avoids making human interference in the natural ecosystem, an exception was made to save the young duck’s life. It was put under the care of Professor Heo and the Facilities Team to regain its health within a month.
In the spring, the healed duck began laying eggs. Professor Heo supported the process by adjusting its diet, avoiding further intervention. On Children’s Day, May 5, the duck’s eggs hatched. The once-isolated duck had become a mother. Ten days later, on May 15, four goslings also hatched from the resident goose flock. With new life flourishing, the pond was more vibrant than ever.
< Rescued baby goslings near the pond, alongside the duck family that took them in. The mother duck—once a vulnerable duckling herself—had grown strong enough to care for others in need. >
But just days later, the mother goose disappeared, and two goslings—still unable to swim—were found shivering by the pond. Dahyeon Byeon, a student from Seoul National University who came for a visit on that day, reported this upon sighting, prompting another rescue. The vulnerable goslings were brought to the shelter to stay with the duck family.
Initially, the interspecies cohabitation was uneasy. But the mother duck did not reject the goslings. Slowly, they began to eat and sleep together, forming a new kind of family. After a month, they were released together into the pond—and to everyone’s surprise, the existing goose flock accepted both the goslings and the duck family.
< A peaceful moment for the duck family. The baby goslings naturally followed the mother duck. >
It took ten months for this family to return. From abandonment and injury to healing, birth, and unexpected bonds, this was more than a story of survival. It was a journey of transformation. The duck family’s ten-month saga is a quiet miracle—written in small moments of crisis, care, and connection—and a lasting memory on the KAIST campus.
< The resident goose flock at KAIST’s pond naturally accepted the returning duck and goslings as part of their group. >
2025.06.10 View 2474 -
New Nanoparticle Drug Combination For Atherosclerosis
Physicochemical cargo-switching nanoparticles (CSNP) designed by KAIST can help significantly reduce cholesterol and macrophage foam cells in arteries, which are the two main triggers for atherosclerotic plaque and inflammation.
The CSNP-based combination drug delivery therapy was proved to exert cholesterol-lowering, anti-inflammatory, and anti-proliferative functions of two common medications for treating and preventing atherosclerosis that are cyclodextrin and statin. Professor Ji-Ho Park and Dr. Heegon Kim from KAIST’s Department of Bio and Brain Engineering said their study has shown great potential for future applications with reduced side effects.
Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of cholesterol and cholesterol-loaded macrophage foam cells in the intima. When this atherosclerotic plaque clogs and narrows the artery walls, they restrict blood flow and cause various cardiovascular conditions such as heart attacks and strokes. Heart attacks and strokes are the world’s first and fifth causes of death respectively.
Oral statin administration has been used in clinics as a standard care for atherosclerosis, which is prescribed to lower blood cholesterol and inhibit its accumulation within the plaque. Although statins can effectively prevent the progression of plaque growth, they have only shown modest efficacy in eliminating the already-established plaque. Therefore, patients are required to take statin drugs for the rest of their lives and will always carry the risk of plaque ruptures that can trigger a blood clot.
To address these issues, Professor Park and Dr. Kim exploited another antiatherogenic agent called cyclodextrin. In their paper published in the Journal of Controlled Release on March 10, Professor Park and Dr. Kim reported that the polymeric formulation of cyclodextrin with a diameter of approximately 10 nanometers(nm) can accumulate within the atherosclerotic plaque 14 times more and effectively reduce the plaque even at lower doses, compared to cyclodextrin in a non-polymer structure.
Moreover, although cyclodextrin is known to have a cytotoxic effect on hair cells in the cochlea, which can lead to hearing loss, cyclodextrin polymers developed by Professor Park’s research group exhibited a varying biodistribution profile and did not have this side effect.
In the follow-up study reported in ACS Nano on April 28, the researchers exploited both cyclodextrin and statin and form the cyclodextrin-statin self-assembly drug complex, based on previous findings that each drug can exert local anti-atherosclerosis effect within the plaque. The complex formation processes were optimized to obtain homogeneous and stable nanoparticles with a diameter of about 100 nm for systematic injection.
The therapeutic synergy of cyclodextrin and statin could reportedly enhance plaque-targeted drug delivery and anti-inflammation. Cyclodextrin led to the regression of cholesterol in the established plaque, and the statins were shown to inhibit the proliferation of macrophage foam cells. The study suggested that combination therapy is required to resolve the complex inflammatory cholesterol-rich microenvironment within the plaque.
Professor Park said, “While nanomedicine has been mainly developed for the treatment of cancers, our studies show that nanomedicine can also play a significant role in treating and preventing atherosclerosis, which causes various cardiovascular diseases that are the leading causes of death worldwide.”
This work was supported by KAIST and the National Research Foundation (NRF) of Korea.
Publications:
1. Heegon Kim, Junhee Han, and Ji-Ho Park. (2020) ‘Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity’ Journal of Controlled Release. Volume 319. Page 77-86. Available online at https://doi.org/10.1016/j.jconrel.2019.12.021
2. Kim, H., et al. (2020) ‘Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy’ ACS Nano. Available online at https://doi.org/10.1021/acsnano.9b08216
Profile: Ji-Ho Park, Ph.D.
Associate Professor
jihopark@kaist.ac.kr
http://openwetware.org/wiki/Park_Lab
Biomaterials Engineering Laboratory (BEL)
Department of Bio and Brain Engineering (BIOENG)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Heegon Kim, Ph.D.
Postdoctoral Researcher
heegon@kaist.ac.kr
BEL, BIOENG, KAIST
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2020.06.16 View 16474