Won+Do+Heo
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KAIST develops technology for selective RNA modification in living cells and animals
· A team led by Professor Won Do Heo from the Department of Biological Sciences, KAIST, has developed a pioneering technology that selectively acetylates specific RNA molecules in living cells and tissues.
· The platform uses RNA-targeting CRISPR tools in combination with RNA-modifying enzymes to chemically modify only the intended RNA.
· The method opens new possibilities for gene therapy by enabling precise control of disease-related RNA without affecting the rest of the transcriptome.
< Photo 1. (From left) Professor Won Do Heo and Jihwan Yu, a Ph.D. Candidate of the Department of Biological Sciences >
CRISPR-Cas13, a powerful RNA-targeting technology is gaining increasing attention as a next-generation gene therapy platform due to its precision and reduced side effects. Utilizing this system, researchers at KAIST have now developed the world’s first technology capable of selectively acetylating (chemically modifying) specific RNA molecules among countless transcripts within living cells. This breakthrough enables precise, programmable control of RNA function and is expected to open new avenues in RNA-based therapeutic development.
KAIST (President Kwang Hyung Lee) announced that a research team led by Professor Won Do Heo in the Department of Biological Sciences has recently developed a groundbreaking technology capable of selectively acetylating specific RNA molecules within the human body using the CRISPR-Cas13 system—an RNA-targeting platform gaining increasing attention in the fields of gene regulation and RNA-based therapeutics.
RNA molecules can undergo chemical modifications—the addition of specific chemical groups—which alter their function and behavior without changing the underlying nucleotide sequence. However, some of these modifications, a critical layer of post-transcriptional gene regulation, remain poorly understood. Among them, N4-acetylcytidine (ac4C) has been particularly enigmatic, with ongoing debate about its existence and function in human messenger RNA (mRNA), the RNA that encodes proteins.
To address this gap, the KAIST research team developed a targeted RNA acetylation system, named dCas13-eNAT10. This platform combines a catalytically inactive Cas13 enzyme (dCas13) that guides the system to specific RNA targets, with a hyperactive variant of the NAT10 enzyme (eNAT10), which performs RNA acetylation. This approach enables precise acetylation of only the desired RNA molecules among the vast pool of transcripts within the cell.
< Figure 1. Development of hyperactive variant eNAT10 through NAT10 protein engineering. By engineering the NAT10 protein, which performs RNA acetylation in human cells, based on its domain and structure, eNAT10 was developed, showing approximately a 3-fold increase in RNA acetylation activity compared to the wild-type enzyme. >
Using this system, the researchers demonstrated that guide RNAs could direct the dCas13-eNAT10 complex to acetylate specific RNA targets, and acetylation significantly increased protein expression from the modified mRNA. Moreover, the study revealed, for the first time, that RNA acetylation plays a role in intracellular RNA localization, facilitating the export of RNA from the nucleus to the cytoplasm—a critical step in gene expression regulation.
To validate its therapeutic potential, the team successfully delivered the targeted RNA acetylation system into the livers of live mice using adeno-associated virus (AAV), a commonly used gene therapy vector. This marks the first demonstration of in vivo RNA modification, extending the applicability of RNA chemical modification tools from cell culture models to living organisms.
< Figure 2. Acetylation of various RNA in cells using dCas13-eNAT10 fusion protein. Utilizing the CRISPR-Cas13 system, which can precisely target specific RNA through guide RNA, a dCas13-eNAT10 fusion protein was created, demonstrating its ability to specifically acetylate various endogenous RNA at different locations within cells. >
Professor Won Do Heo, who previously developed COVID-19 treatment technology using RNA gene scissors and technology to activate RNA gene scissors with light, stated, "Existing RNA chemical modification research faced difficulties in controlling specificity, temporality, and spatiality. However, this new technology allows selective acetylation of desired RNA, opening the door for accurate and detailed research into the functions of RNA acetylation." He added, "The RNA chemical modification technology developed in this study can be widely used as an RNA-based therapeutic agent and a tool for regulating RNA functions in living organisms in the future."
< Figure 3. In vivo delivery of targeted RNA acetylation system. The targeted RNA acetylation system was encoded in an AAV vector, commonly used in gene therapy, and delivered intravenously to adult mice, showing that target RNA in liver tissue was specifically acetylated according to the guide RNA. >
This research, with Ph.D. candidate Jihwan Yu from the Department of Biological Sciences at KAIST as the first author, was published in the journal Nature Chemical Biology on June 2, 2025. (Title: Programmable RNA acetylation with CRISPR-Cas13, Impact factor: 12.9, DOI: https://doi.org/10.1038/s41589-025-01922-3)
This research was supported by the Samsung Future Technology Foundation and the Bio & Medical Technology Development Program of the National Research Foundation of Korea.
2025.06.10 View 318 -
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 390 -
Life Springs at KAIST: A Tale of Two Special Campus Families
A Gift of Life on Teachers' Day: Baby Geese Born at KAIST Pond
On Teachers' Day, a meaningful miracle of life arrived at the KAIST campus. A pair of geese gave birth to two goslings by the duck pond.
< On Teachers' Day, a pair of geese and their goslings leisurely swim in the pond. >
The baby goslings, covered in yellow down, began exploring the pond's edge, scurrying about, while their aunt geese steadfastly stood by. Their curious glances, watchful gazes, playful hops on waterside rocks, and the procession of babies swimming behind their parents in the water melted the hearts of onlookers.
< As night falls on the duck pond, the goose family gathers among the reeds. >
This special new life, born on Teachers' Day, seems to symbolize the day's meaning of "care" and "growth." This wondrous scene of life brought warm comfort and joy to KAIST members, adding the inspiration of nature to a campus that is a space for research and learning.
< Under the protection of the adult geese, the goslings take their first steps, exploring the pond's grassy areas and rocks. >
This adorable family is already roaming the area leisurely, like the pond's owners. With the joy of life added to the spring-filled pond, warm smiles are spreading across the KAIST campus.
< The geese look around, surveying their surroundings, while caring for their goslings. >
The pond has now become a small but special haven for students and staff. This goose family, arriving on Teachers' Day, quietly reminds us of the meaning of care and learning conveyed by nature.
< The goose family shows care and growth, and warm moments together are anticipated. >
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On Children's Day 2025, a Duck Becomes a Mother
In July 2024, a special guest arrived at the KAIST campus. With soft yellow down, waddling gait, and a flat beak, it was undeniably a baby duck. However, for some reason, its mother was nowhere to be seen. Given that it wasn't afraid of people and followed them well, it was clear that someone had abandoned the duck.
Fortunately, the baby duck was safely rescued thanks to prompt reporting by students.
< Two ducks found on a corner of campus, immediately after their rescue in summer 2024. >
The ducks, newly integrated into KAIST, seemed to adapt relatively peacefully to campus life. As new additions, they couldn't blend in with the existing goose flock that had settled on campus, but the geese didn't ostracize them either. Perhaps because they were awkward neighbors, there was hope that the ducks would soon join the existing goose flock.
< Following their rescue based on a student's report in summer 2024, the ducks adapted to campus life under the protection of the campus facility team and Professor Won Do Heo. >
Professor Won Do Heo of the Department of Biological Sciences, widely known as "Goose Dad," stepped forward to protect them along with the KAIST facility team. Professor Heo is well-known for consistently observing and protecting the campus geese and ducks, which are practically symbols of KAIST. Thanks to the care of the staff and Professor Heo, the two ducks were safely released back onto campus approximately one month after their rescue.
< A moment on campus: Before winter, the ducks lived separately from the goose flock, maintaining a certain distance. While there were no conflicts, they rarely socialized. >
However, as winter passed, sad news arrived. One duck went missing, and the remaining one was found injured by the pond. While the policy of the facility team and Professor Heo was to minimize intervention to allow campus animals to maintain their natural state, saving the injured duck was the top priority. After being isolated again for a month of recovery, the duck fully recovered and was able to greet spring under the sun.
< The mother duck left alone in winter: One went missing, and the remaining one was found injured. After indoor isolation and recovery, she was released back onto campus in the spring. >
As spring, the ducks' breeding season, began, Professor Heo decided to offer a little more help. When signs of egg-laying appeared, he consistently provided "special meals for pregnant mothers" throughout March. On the morning of May 5th, Children's Day, 28 days after the mother duck began incubating her eggs with the care and attention of KAIST members, new life finally hatched. It was a precious outcome achieved solely by the duck that had survived abandonment and injury, with no special protection other than food.
The duck, having overcome hardship and injury to stand alone, has now formed a new family. Although there is still some distance from the existing goose flock, it is expected that they will naturally find their place in the campus ecosystem, as KAIST's geese are not aggressive or exclusive. The KAIST goose flock already has experience protecting and raising five ducklings.
< A new beginning by the pond on Children's Day: On the morning of May 5th, the 28th day of incubation, four ducklings hatched by the pond. This was a natural hatching, achieved without protective equipment. >
A single duck brought a special spring to the KAIST campus on Children's Day. The outcome achieved by that small life, leading to the birth of a new family, also symbolizes the harmonious coexistence of people and animals on the KAIST campus. The careful intervention of KAIST members, providing only the necessary assistance from rescue to hatching, makes us reconsider what "desirable coexistence between animals and people" truly means.
2025.05.21 View 1252 -
A KAIST Research Team Observes the Processes of Memory and Cognition in Real Time
The human brain contains approximately 86 billion neurons and 600 trillion synapses that exchange signals between the neurons to help us control the various functions of the brain including cognition, emotion, and memory. Interestingly, the number of synapses decrease with age or as a result of diseases like Alzheimer’s, and research on synapses thus attracts a lot of attention. However, limitations have existed in observing the dynamics of synapse structures in real time.
On January 9, a joint research team led by Professor Won Do Heo from the KAIST Department of Biological Sciences, Professor Hyung-Bae Kwon from Johns Hopkins School of Medicine, and Professor Sangkyu Lee from the Institute for Basic Science (IBS) revealed that they have developed the world’s first technique to allow a real-time observation of synapse formation, extinction, and alterations.
Professor Heo’s team conjugated dimerization-dependent fluorescent proteins (ddFP) to synapses in order to observe the process in which synapses create connections between neurons in real time. The team named this technique SynapShot, by combining the words ‘synapse’ and snapshot’, and successfully tracked and observed the live formation and extinction processes of synapses as well as their dynamic changes.
< Figure 1. To observe dynamically changing synapses, dimerization-dependent fluorescent protein (ddFP) was expressed to observe flourescent signals upon synapse formation as ddFP enables fluorescence detection through reversible binding to pre- and postsynaptic terminals. >
Through a joint research project, the teams led by Professor Heo and Professor Sangkyu Lee at IBS together designed a SynapShot with green and red fluorescence, and were able to easily distinguish the synapse connecting two different neurons. Additionally, by combining an optogenetic technique that can control the function of a molecule using light, the team was able to observe the changes in the synapses while simultaneously inducing certain functions of the neurons using light.
Through more joint research with the team led by Professor Hyung-Bae Kwon at the Johns Hopkins School of Medicine, Professor Heo’s team induced several situations on live mice, including visual discrimination training, exercise, and anaesthesia, and used SynapShot to observe the changes in the synapses during each situation in real time. The observations revealed that each synapse could change fairly quickly and dynamically. This was the first-ever case in which the changes in synapses were observed in a live mammal.
< Figure 2. Microscopic photos observed through changes of the flourescence of the synapse sensor (SynapShot) by cultivating the neurons of an experimental rat and expressing the SynapShot. The changes in the synapse that is created when the pre- and post-synaptic terminals come into contact and the synapse that disappears after a certain period of time are measured by the fluorescence of the SynapShot. >
Professor Heo said, “Our group developed SynapShot through a collaboration with domestic and international research teams, and have opened up the possibility for first-hand live observations of the quick and dynamic changes of synapses, which was previously difficult to do. We expect this technique to revolutionize research methodology in the neurological field, and play an important role in brightening the future of brain science.”
This research, conducted by co-first authors Seungkyu Son (Ph.D. candidate), Jinsu Lee (Ph.D. candidate) and Dr. Kanghoon Jung from Johns Hopkins, was published in the online edition of Nature Methods on January 8 under the title “Real-time visualization of structural dynamics of synapses in live cells in vivo”, and will be printed in the February volume.
< Figure 3. Simultaneous use of green-SynapShot and red-SynapShot to distinguish and observe synapses with one post-terminal and different pre-terminals. >
< Figure 4. Dimer-dependent fluorescent protein (ddFP) exists as a green fluorescent protein as well as a red fluorescent protein, and can be applied together with blue light-activated optogenetic technology. After activating Tropomyosin receptor kinase B (TrkB) by blue light using optogenetic technology, the strengthening of synaptic connections through signals of brain-derived neurotrophic factor is observed using red-SynapShot. >
< Figure 5. Micrographs showing real-time changing synapses in the visual cortex of mice trained through visual training using in vivo imaging techniques such as two-photon microscopy as well as at the cellular level. >
This research was supported by Mid-Sized Research Funds and the Singularity Project from KAIST, and by IBS.
2024.01.18 View 6589 -
Professor Won Do Heo Receives 'Scientist of the Month Award'
Professor Won Do Heo of the Department of Biological Sciences was selected as the “Scientist of the Month” for April 2017 by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea.
Professor Heo was recognized for his suggestion of a new biological research method developing various optogenetics technology which controls cell function by using light. He developed the technology using lasers or LED light, without the need for surgery or drug administration, to identify the cause of diseases related to calcium ions such as Alzheimer’s disease and cancer.
The general technique used in optogenetics, that control cells in the body with light, is the simple activation and deactivation of neurons.
Professor Heo developed a calcium ion channel activation technique (OptoSTIM1) to activate calcium ions in the body using light. He also succeeded in increasing calcium concentrations with light to enhance the memory capacity of mice two-fold.
Using this technology, the desired amount and residing time of calcium ion influx can be controlled by changing light intensity and exposure periods, enabling the function of a single cell or various cells in animal tissue to be controlled remotely.
The experimental results showed that calcium ion influx can be activated in cells that are affected by calcium ions, such as normal cells, cancer cells, and human embryonic stem cells. By controlling calcium concentrations with light, it is possible to control biological phenomena, such as cellular growth, neurotransmitter transmission, muscle contraction, and hormone control.
Professor Heo said, “Until now, it was standard to use optogenetics to activate neurons using channelrhodopsin. The development of this new optogenetic technique using calcium ion channel activation can be applied to various biological studies, as well as become an essential research technique in neurobiology.
The “Scientist of the Month Award” is given every month to one researcher who made significant contributions to the advancement of science and technology with their outstanding research achievement. The awardee will receive prize money of ten million won.
2017.04.07 View 9324