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KAIST Identifies a “Hidden Amplification Switch” in Lymphangiogenic Signaling
Lymphatic vessels act as the body’s “drainage system,” collecting excess fluid from tissues. When lymphatic drainage is impaired because lymphatic vessels are underdeveloped, damaged, or dysfunctional, lymphedema can develop, causing swelling, particularly in the arms and legs. Conversely, excessive lymphatic vessel growth around tumors can facilitate cancer metastasis by providing routes for tumor cells to spread. Korean researchers have discovered that VEGF-C brings two VEGFR-3 receptors together, and the resulting VEGF-C–VEGFR-3 complexes further cluster to amplify signaling. Targeting this clustering process may provide a new strategy for either enhancing or suppressing lymphangiogenic signaling, depending on the disease context.
KAIST (President Choongsik Bae) announced on October 2 that a joint research team led by Professor Ho Min Kim from the Department of Biological Sciences at KAIST and Dr. Sangkyu Lee of the Institute for Basic Science (IBS; President Suk Bok Chang) determined the three-dimensional structure of the VEGF-C–VEGFR-3 complex and identified how higher-order clustering of these complexes amplifies signaling.
When VEGF-C binds to VEGFR-3 on the cell surface, the receptor is activated and signals that regulate the formation and function of lymphatic vessels are transmitted into the cell. Until now, VEGF-C-mediated dimerization of two VEGFR-3 receptors has been considered a key step in receptor activation. However, how the signal becomes further amplified after this step has not been fully understood.
The research team examined the structure of VEGF-C bound to VEGFR-3 using cryogenic electron microscopy (cryo-EM), which enables detailed visualization of the three-dimensional structures of proteins. They found that VEGF-C-induced complexes containing two VEGFR-3 receptors further assembled side by side into higher-order clusters. This revealed a new structural mode by which VEGF-C–VEGFR-3 complexes can organize laterally along the cell membrane.Simply put, it is like two people first forming a team to begin a task, and then multiple teams gathering together to increase their collective strength. The researchers also tested whether this clustering actually amplifies signaling. By altering the regions where the complexes contact one another and by using light to control receptor clustering, they confirmed that the gathering of multiple complexes plays an important role in signal amplification.
This study identifies a new point at which lymphangiogenic signaling could potentially be regulated. In the future, researchers may explore ways to enhance signaling when lymphatic vessel formation is insufficient and to suppress signaling when excessive lymphatic vessels form around tumors. However, this study did not demonstrate therapeutic effects for lymphedema or the inhibition of cancer metastasis, and further research will be required before the findings can be applied to actual treatments.
Professor Ho Min Kim said, “This study reveals how two VEGFR-3 receptors first form a ligand-induced pair, after which multiple such complexes cluster together to further amplify the signal for lymphangiogenesis ,” adding, “By identifying this previously unseen ‘hidden amplification switch’ in lymphangiogenic signaling, we expect this work to provide an important foundation for developing new therapeutic strategies for related diseases such as lymphedema and cancer metastasis.”
Dr. Ryeongeun Cho of the KAIST InnoCORE AI-CRED Innovative Drug Research Group and Dr. Jinsook Ahn of the KAIST Department of Biological Sciences participated in the study as co-first authors. Professor Ho Min Kim of KAIST and Dr. Sangkyu Lee of IBS led the research as co-corresponding authors. The findings were published online on September 9 in the international journal Advanced Science.
Paper title: Structural Basis of Lymphangiogenic Receptor VEGFR-3 Activation Mediated by Distinctive Clustering of the Ligand–Receptor Complex, DOI: 10.1002/advs.77728
Related videos:
Video showing cryo-EM sample preparation by rapidly freezing protein samples at cryogenic temperatures: https://drive.google.com/file/d/1OGPpkzmZMaWU3oxfswpbcEtt3NzX3n4q/view?usp=drive_link
Video showing the grid screening process for cryo-EM image collection: https://drive.google.com/file/d/1Bg6zEPeS9NZDO8zFaj59Fe7L_f8tBWwQ/view?usp=drive_link
Video showing the loading of frozen protein samples into the cryo-EM instrument: https://drive.google.com/file/d/19c1INwek38B72KKPPXmPVTggYAoO4aY3/view?usp=drive_link
Titan Krios cryo-EM instrument installed at KAIST KARA: https://drive.google.com/file/d/1c5Wmj44_9taYIW4N_mumg6tT21iOUYNQ/view?usp=drive_link
Video of the molecular structure of the VEGF-C and VEGFR-3 complex identified in this study: https://drive.google.com/file/d/198bcFoTb_pv__Ep-MHwcI47G4gv5yisx/view?usp=drive_link
This work was supported by the National Research Foundation of Korea (RS-2024-00397681, RS-2025-00523615 to H.M.K. and RS-2025-00523575 to J.A.), the InnoCORE program of the Ministry of Science and ICT (N10250153 to H.M.K. and R.C.), the NEXUS & CELINE consortium, the KAIST Convergence Research Institute Operation Program, and the Institute for Basic Science (IBS-R001-Y4 to S.L.), among others.
2026.10.02 View 1030 -
KAIST Develops a Genetic Switch That Works in Both Bacteria and Yeast
Microbial cell factories that produce pharmaceutical ingredients and other useful compounds include both the bacterium Escherichia coli and yeast, the organism used to leaven bread and ferment alcohol. The two organisms turn genes on by different rules, so a production design built for one has been hard to transfer to the other. A KAIST research team has now built a gene control element that works in both and tested it using a green pigment whose production requires several genes working together. The work is expected to help researchers select the microbe best suited to producing a target compound.
KAIST (President Choongsik Bae) announced on September 28 that a research team led by Professor Juyoung Lee from the Graduate School of Engineering Biology has developed a "hybrid promoter," a gene control element that works in both E. coli and yeast, two very different types of microorganism.
For a microbe to make a target compound, the genes responsible for producing it must be turned on. A promoter is the stretch of DNA located in front of a gene that controls how strongly that gene works.
The challenge is that E. coli and yeast turn genes on in different ways, and a promoter that performs well in E. coli may not work at all in yeast. Making the same compound in a different microbe has therefore required choosing a promoter suited to that host and retuning the output of each gene from the beginning.
The team's hybrid promoter combines, within a single sequence, DNA elements that E. coli and yeast each recognize. It is, in effect, a shared control element designed so that each organism can find the signals it needs even though the two read genes differently. By varying the combination of these elements, the researchers built a series of promoters spanning a range of strength from weak to strong.
The promoters worked in both hosts, and combinations that were strong in E. coli were generally strong in yeast as well. That does not mean the two microbes make equal amounts of a compound; it means the relative ranking of promoter strengths from weak to strong is preserved across hosts.
The team then tested whether the new control element could do more than turn on a single gene and could also be used for actual compound production. For this, they chose a green pigment whose production requires three genes acting in sequence. Under the strong control element, pigment output was about 3.1 times higher in E. coli and about 2.6 times higher in yeast than under the weak one. The result shows that the system can control the amount of a compound produced in both microbes. The team also confirmed that the promoters worked in other types of bacteria and yeast.
The approach could help researchers identify which microbe is best suited to producing a given compound, since the same gene control design can be applied across several microbes and the production results can be compared. It may reduce the need to redesign control elements from scratch whenever the host changes, although improving actual output will still require host-specific tuning.
"What matters about this work is that it gives us a common design principle, one that lets us predict a promoter's relative strength even when the microbe changes," said Professor Juyoung Lee. She added that she expects the approach to speed up biomanufacturing by making it faster to design and compare a range of microbial cell factories.
So-Hee Son, Soo Young Moon, and Nan-Yeong An of KAIST are co-first authors on the paper, which was published in Nucleic Acids Research on September 23 and first appeared online on September 8.
Paper title: Modular synthetic cross-kingdom promoters enable coordinated expression in Escherichia coli and Saccharomyces cerevisiae,
DOI: https://doi.org/10.1093/nar/gkag868
This work was supported by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF) through the Bio & Medical Technology Development Program (RS-2024-00445145) and the Basic Science Research Program (RS-2025-00518119), with additional support from the Korea-US Collaborative Research Fund (KUCRF), funded by MSIT and the Ministry of Health & Welfare (RS-2024-00468410).
2026.09.28 View 1694 -
KAIST Finds a Way to Redirect Cell Fate with Just a Single Stimulus
Which genes need to be controlled to guide a stem cell toward a desired cell type, or to modulate an immune cell's inflammatory response? A Korean research team has developed a general-purpose computational framework that identifies the key targets needed to steer a cell toward a desired state with a single temporary intervention, without permanently altering its genes.
KAIST (President Choongsik Bae) announced on September 23 that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering has developed NUDGE, a foundational technology that redirects cell fate in a desired direction through a minimal, temporary intervention by harnessing the gene regulatory dynamics already present within cells.
Technologies that redirect cell fate have drawn attention as key tools for treating intractable diseases and advancing regenerative medicine, since they can be used to differentiate stem cells into cells with specific functions or to return diseased or aged cells to a near-normal state. Differentiation, for example, refers to the process by which a stem cell becomes a specific cell type with a distinct function, such as a cardiomyocyte or a neuron.
However, existing methods for controlling cell fate have relied mainly on permanent intervention like keeping specific genes locked in an "on" or "off" state. While this approach can produce the desired cell state, it has a limitation. It can reduce plasticity, the flexibility that allows cells to adapt to future changes in their environment, and it can also give rise to abnormal cell states that do not exist in nature.
Rather than forcing a cell into a fixed state, the research team devised a new strategy that lets the cell reach the desired state on its own through a single temporary stimulus. The approach nudges the gene regulatory dynamics already present inside the cell toward the target direction, much like briefly clearing a blocked channel and letting the water find its own course.
NUDGE (natural dynamics control of gene regulatory networks), the technology the team developed, uses a computational logic model to examine how key genes inside a cell influence one another and to determine which state the cell ultimately reaches as a result. It then mathematically decomposes the logical functions that describe these gene interactions to identify the minimal combination of control factors needed to convert a cell from its current state to the desired one.
For example, if the goal is to differentiate a stem cell into a cardiomyocyte, NUDGE functions as a "blueprint for minimal intervention" that identifies which molecular targets need to be temporarily activated or inhibited.
A key strength of the framework is that its exact method is mathematically guaranteed to identify all minimal control combinations that lead to the desired phenotype within the model. The team also presented an efficient approximation method that extends the framework to large-scale molecular networks.
NUDGE does more than identify which factors to stimulate. It can also analyze which pathways a stimulated cell follows to reach the target state and how stably that state is maintained once reached, making it possible to anticipate whether unexpected states might emerge during the transition.
The researchers assessed permanent control in 63 published biological network models where fixing a single node was sufficient to achieve the target phenotype; 55 showed reduced plasticity or attractors absent from the uncontrolled network. Separately, NUDGE's approximation achieved an average intervention error below 0.01 in more than 90 percent of 552 control problems across 69 large biological networks. Error measured the fraction of simulated converged states with the undesired phenotype. Of the minimum-sized, error-free interventions pooled from the three methods for each problem, NUDGE found an average of 83 percent, compared with 59 percent for IBMFA and 53 percent for LDOI.
To assess how well NUDGE explains real biological phenomena, the researchers applied it to three distinct processes: cardiomyocyte differentiation, fate determination in mast cells involved in allergic responses, and the conversion of macrophages, a type of immune cell, into an anti-inflammatory state.
In cardiomyocyte differentiation, the framework reproduced the known pattern in which MESP1, a gene important for heart development and regeneration, is briefly active early in differentiation but inactive in mature cardiomyocytes. The model shows how a single temporary intervention involving MESP1 and another regulatory target can guide differentiation without keeping MESP1 continuously active.
The team also identified GATA2 and GATA1 as key regulators of cell fate during mast cell formation. In the macrophage model, the team derived optimal strategies for a single temporary intervention, including one using IL-4, to induce anti-inflammatory M2 states while preserving the capacity to transition between inflammatory and anti-inflammatory phenotypes and among M2 subtypes.
The significance of this technology lies in providing a general-purpose framework that identifies where a single temporary intervention can guide a cell to a desired state, provided that a stable state with the desired phenotype exists in the network's uncontrolled dynamics. It is expected to find broad application, from guiding normal stem cells to differentiate into specific cell types such as cardiomyocytes, to normalizing diseased or aged cells, regenerating damaged tissue, modulating immune responses, and designing cancer reversion therapies that return cancer cells to a near-normal state.
Professor Cho said, "NUDGE is not a technology limited to returning a specific cell to a healthy state, but a general-purpose cell-control technology that guides a cell from its current state to a desired state through a single minimal stimulus." He added that the technology is expected to serve as a foundational tool for designing new control strategies across stem cell differentiation, aging, autoimmune disease, regenerative medicine, and cancer reversion therapy.
The study was conducted by Ferio Brahmana, who holds a master's degree, and Corbin Hopper, a PhD student, both in KAIST's Department of Bio and Brain Engineering, who contributed equally as co-first authors, with PhD student Woojeong Lee as a co-author. The findings were published online on September 14 in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Paper Title: Uncovering minimal control of cell fate by natural dynamics,
DOI: 10.1073/pnas.2604777123
This work was supported by National Research Foundation of Korea grants funded by the Korea Government, the Ministry of Science and Information and Communication Technology (ICT) (RS-2023-NR077224, RS-2024-00405360, RS-2025-17652976, and 2021M3A9I4024447 [Bio & Medical Technology Development Program]). It was also supported by a grant of the Korea Dementia Research Project through the Korea Dementia Research Center, funded by the Ministry of Health & Welfare and the Ministry of Science and ICT, Republic of Korea (RS-2025-02264017) and by the Korea Advanced Institute of Science and Technology (KAIST) Quantum+X Convergence R&D Project and KAIST Grand Challenge 30 Project.
2026.09.23 View 3482 -
KAIST Researchers Uncover How Neurons Deliver RNA to Where It Is Needed
Much like a courier reading an address on a package, neurons must deliver RNA to the precise locations where it is needed. A KAIST research team has discovered how a small chemical modification on RNA acts as a “delivery tag,” helping selected RNAs travel to distant regions of neurons.
The findings provide a basis for investigating RNA “delivery errors” in brain disorders—cases in which RNA is produced normally but fails to reach its intended destination—and may ultimately inform the development of new therapeutic strategies.
KAIST (President Choongsik Bae) announced on September 14 that a research team led by Professor Ki-Jun Yoon of the Department of Biological Sciences has identified a mechanism through which N6-methyladenosine, or m6A, facilitates the transport of specific RNAs to distal axons, the long, cable-like projections of neurons.
Unlike most other cells, neurons have long, highly branched extensions. Axons transmit signals to other neurons, while dendrites receive incoming signals. For the brain to develop and function normally, these structures must grow properly and form appropriate connections.
Because neurons can extend over considerable distances, RNA produced in the cell body may be needed far away, including at the growing tip of an axon. Neurons must therefore identify particular RNAs among thousands of candidates and transport them to the correct subcellular locations.
Just as producing a package does not complete its delivery—the package must also reach the correct address—producing RNA is only part of the process. RNA must arrive at the right place at the right time. However, the mechanisms through which neurons select and transport RNAs over long distances have remained incompletely understood.
The research team found that m6A, a small chemical modification added to RNA, plays an important role in this process. m6A is a modification of adenosine, one of the building blocks of RNA, and is known to influence several aspects of RNA metabolism, including stability and translation. The new study shows that m6A can also function as a molecular “delivery tag” that promotes the transport of specific RNAs to distal regions of neurons.
The researchers first examined mice in which Mettl14, a component of the enzyme complex that installs m6A on RNA, was deleted from developing neurons. In the absence of normal m6A modification, the neurons exhibited impaired axon projection and neurite development. These findings confirmed that m6A plays an important role in the early development of neurons.
The team then used a high-resolution technique known as m6A-SAC-seq to map the precise locations of m6A modifications in RNA from the developing mouse brain at single-nucleotide resolution. The resulting map revealed that RNAs associated with axon development and synapse organization were among those marked by m6A.
The researchers also identified how this “delivery tag” is recognized and connected to the cellular transport machinery. They found that YTHDF2, a protein that recognizes m6A-modified RNA, works with the RNA-binding protein FMRP and the motor protein KIF5C to facilitate the transport of RNA along neuronal processes.
In the delivery analogy, m6A serves as the tag attached to the RNA, YTHDF2 reads the tag, and FMRP and KIF5C help connect the RNA to the cellular machinery that carries it toward its destination.
YTHDF2 has previously been studied primarily for its role in promoting the degradation of RNA that is no longer needed. This study reveals an additional function: in developing neurons, YTHDF2 also helps transport specific RNAs to distal locations rather than simply directing them toward degradation.
The findings offer a new perspective on the study of brain disorders. Research has traditionally focused on whether RNA is produced and maintained correctly. The new results suggest that researchers should also consider whether normally produced RNA is delivered to the correct location within a neuron.
In other words, neurological dysfunction may potentially arise not only from defects in RNA itself, but also from problems with the molecular tags or transport machinery that determine where the RNA travels.
Future studies could investigate whether such RNA delivery errors occur in neurodevelopmental or neurodegenerative disorders and whether they contribute to neuronal dysfunction or disease onset. If such links are established, the findings could eventually support the development of therapeutic approaches that regulate RNA transport and restore the delivery of specific RNAs to their intended locations.
The high-resolution m6A map of the developing nervous system generated in this study may also serve as a valuable resource for examining how RNA modification and intracellular transport change during brain aging and neurodegenerative disease.
“Our study shows that a small chemical modification on RNA does more than regulate RNA stability—it also plays an important role in delivering specific RNAs to the locations where they are needed within neurons,” said Professor Yoon. “We hope these findings will provide a foundation for understanding why RNA may fail to reach its intended destination in brain disorders and for exploring new therapeutic possibilities.”
Bonsang Koo, Dr. Ajeet Kumar, and Huiseon Hwang of the KAIST Department of Biological Sciences contributed equally to the study as co-first authors. The paper was published in Nature Communications on July 30.
Paper title: The m⁶A reader YTHDF2 regulates mRNA transport and axon outgrowth in developing neurons
DOI: 10.1038/s41467-026-76161-8
Author information: Co-first authors (Bonsang Koo, Ajeet Kumar, Huiseon Hwang); Contributing authors (Minyeong Park, Sung-Min Lee, Ki-Heon Lee, Ji-Hoon Moon, Jaewon Yang, Chan-Woo Park, Saebom Lee, Hee-Jung Jo, Woo-il Kim, Eunji Cho, Hagyeong Lee, Chang-Won Lee, Jae-Sung Woo, Jong Hyuk Yoon, Yoon Ki Kim); Corresponding author (Ki-Jun Yoon)
This work was supported by National Research Foundation of Korea (NRF) grants (2020M3A9E403967022, RS-2024-00332454, RS-2024-00440778, and RS-2026-25488918 to K.-J.Y.) funded by the Korean Ministry of Science and ICT, and Future Planning (MSIP), the POSCOScience Fellowship from the POSCO TJ Park Foundation (to K.-J.Y.), the Young Investigator Grant from the Suh Kyungbae Foundation (to K.-J.Y.), the Korea Brain Research Institute (KBRI) Basic Research Program through the Korea Brain Research Institute, funded by the Ministry of Science and ICT (MSIT) (24-BR-02-03 to J.H.Y).
2026.09.14 View 3896 -
KAIST Develops AI That Can Sense “That’s Not What I Meant” Without Being Told
A future in which AI can recognize a person’s unspoken “that’s not what I meant” response from brain signals and adjust its behavior on its own is coming closer. KAIST researchers have developed a technology that detects cognitive mismatch between humans and AI through brainwaves, enabling AI systems to revise their actions in real time according to human goals. The achievement is expected to accelerate the shift from AI that follows explicit commands to AI that can infer human intent.
KAIST (President Choongsik Bae) announced on September 11 that a research team led by Endowed Chair Professor Sang Wan Lee of the Department of Brain and Cognitive Sciences (Director of the Center for Neuroscience-Inspired Artificial Intelligence), in collaboration with Microsoft Research Asia (MSRA), has developed Neural Value Alignment (NVA), a next-generation brain–computer interface (BCI) technology that uses human brainwaves to align AI behavior with human intentin real time.
For AI to collaborate naturally with people, it must accurately understand what a person actually wants. Until now, however, AI systems have largely inferred human intent from externally observable information such as speech, actions, or gestures.
The challenge is that the same action can reflect different goals, and the same goal can also be achieved through different actions. For example, when a person picks up a cup, it may be unclear whether they intend to drink from it or hand it to someone else. Conversely, if the person's goal is simply to quench their thirst, that same goal could be pursued through several different actions — reaching for the cup, picking up a water bottle, or asking someone else to bring a drink. Because of this two-sided “goal–action ambiguity,” when AI misunderstands human intent, users often have to correct it through additional commands or actions.
To address this problem, the research team focused on the “prediction error” signals that arise unconsciously in the brain when a person encounters an unexpected situation. In simple terms, the team used the brain’s instant “that’s not what I meant” response when AI performs the wrong action or pursues the wrong goal.
The researchers distinguished between two types of brain responses. The first is reward prediction error (RPE), which appears when AI misunderstands the person’s ultimate goal. The second is state prediction error (SPE), which appears when the goal is correct but the process or method of action differs from what the person expected.
The team measured real-time electroencephalography (EEG) signals from people as they observed AI performing tasks. They found that the brain produced different signals depending on whether the AI misunderstood the goal itself or chose the wrong method while pursuing the correct goal. The researchers also identified distinctive brainwave patterns that appeared when both types of errors occurred simultaneously.
By applying deep learning to these brain signals, the team developed a technology that can determine, from EEG alone, how a person is interpreting the AI’s behavior. In other words, even without a person saying “that’s wrong,” the AI can recognize whether the human brain is signaling that “the goal is wrong” or “the method is wrong.”
The team then proposed a Neural Value Alignment-based human–AI synergy algorithm, which feeds these decoded brain signals back to the AI in real time so that it can correct its own behavior.
When the AI detects an SPE signal, it interprets the situation as “the desired goal is correct, but the method is wrong” and adjusts its action strategy. When it detects an RPE signal, it understands that “the goal itself was misunderstood” and searches again for what the person truly intended.
Simulation results showed that the proposed method adapted more quickly than existing approaches even in uncertain situations, such as when a person’s goal suddenly changed or some human neural feedbacks were missing.
The key significance of this research is that it demonstrates the possibility of AI systems correcting themselves by reading a person’s unconscious “that’s not what I meant” brain response, without requiring the user to repeatedly say “do it this way” or “that’s not right.”
As the technology advances, it could be applied to physical AI robots in homes and industrial settings, allowing them to understand user intent more naturally and adjust their actions accordingly. It could also be extended to autonomous vehicles that quickly reflect driver judgment, medical and rehabilitation robots for patients who have difficulty speaking or moving, and educational AI systems that adapt to a student’s cognitive state.
Ultimately, the study presents a new model of human–AI collaboration, moving beyond AI that acts only when explicitly instructed toward AI that can sense human responses and adjust itself accordingly.
Professor Sang Wan Lee, who led the international collaboration, said, “This research is meaningful because it shows that AI can move beyond inferring human intent only from visible behavioral outcomes and instead directly use cognitive signals generated in the brain during collaboration with AI.” He added, “The technology can be expanded to a wide range of fields where human judgment and AI behavior must be closely connected, including physical AI, BCI, autonomous driving, precision personalized education, medical robotics, and human–computer interaction.”
Miran Lee, Director, Microsoft Research Accelerator at Microsoft Research, said, “This achievement is the result of the ongoing international collaboration between KAIST and Microsoft Research Asia. We look forward to continuing this partnership to develop world-class BCI technologies that enable humans and AI to communicate and collaborate more naturally.”
The study’s first author is Xin Xu, a Ph.D. student in KAIST’s Department of Brain and Cognitive Sciences. Researchers from Microsoft Research Asia, including Yansen Wang, Dongqi Han, and Dongsheng Li, also participated in the study. The research was published online in August 2026 in IEEE Transactions on Cybernetics, an international journal in the field of cybernetics.
Paper title: Neural Value Alignment: Human–AI Collaboration Under Goal–Action Ambiguity
DOI: 10.1109/TCYB.2026.3722605
Another KAIST–Microsoft Research Asia collaborative study on helping AI rapidly adapt to continuously changing environments was presented in June at ICML 2026, one of the leading international conferences in artificial intelligence. The study was led by Niklas Koeppe, a Ph.D. student in KAIST’s Program of Brain and Cognitive Engineering, as first author.
Paper title: Mitigating Plasticity Loss through Architectural Design in Continual Learning
Original paper: https://icml.cc/virtual/2026/poster/61534
This research was supported by the Institute of Information & Communications Technology Planning & Evaluation (IITP), funded by the Ministry of Science and ICT.
2026.09.10 View 3161 -
Vitamin A Derivative Preserves T Cells’ Function as KAIST Points to a New Strategy for Treating Intractable Brain Tumors
Immune cells can become exhausted after prolonged exposure to cancer, gradually losing their ability to attack tumor cells. This phenomenon is particularly pronounced in aggressive brain tumors and can severely limit the effectiveness of immunotherapy. A KAIST research team has now discovered that all-trans retinoic acid (ATRA), a vitamin A derivative, may help prevent such exhaustion and enhance the efficacy of immune checkpoint inhibitors.
KAIST (President Choongsik Bae) announced on September 8 that a research team led by Professor Heung Kyu Lee from the Department of Biological Sciences, in collaboration with researchers from Seoul St. Mary's Hospital, and Konyang University College of Medicine, has found that all-trans retinoic acid (ATRA), a form of active vitamin A metabolite, suppresses the "terminal exhaustion" of CD8⁺ T cells that attack cancer cells within brain tumors, and can enhance the effect of anti-PD-1 immunotherapy. Anti-PD-1 is a leading immuno-oncology drug (immune checkpoint inhibitor).
Glioblastoma is a representative form of intractable brain cancer that frequently recurs even after surgery, radiation, and chemotherapy. Immune checkpoint inhibitors have shown only limited effect against the disease. One key reason is that immune cells that infiltrate the tumor become exhausted after prolonged combat and lose their functional capacity.
Cells that reach a state of terminal exhaustion in particular lose their ability to kill cancer cells, much like soldiers who have exhausted themselves in prolonged combat. In this state, achieving sufficient therapeutic effect is difficult even with anti-PD-1 therapy, which releases the "brake" cancer cells impose on immune cells.
To address this problem, the research team tried to figure out how to prevent immune cells from reaching total burnout, rather than how to revive the cells. Subsequently, the research team focused on the signaling of ATRA, an active vitamin A metabolite known to regulate cell differentiation and function.
Using an in-vitro model that mimicked the hypoxic, exhaustion-promoting tumor microenvironment of brain tumors, the team induced exhaustion in CD8⁺ T cells. Those conditioned with ATRA progressed to terminal exhaustion at a markedly lower rate. These cells also produced higher levels of immune molecules essential for attacking cancer — including interleukin-2 (IL-2), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) — and retained their ability to kill brain tumor cells.
The team also confirmed that ATRA activates WNT/β-catenin signaling within CD8⁺ T cells and increases TCF-1βBD, a TCF-1 isoform important for maintaining T-cell function. In simple terms, the vitamin A metabolite turns on a "function-preserving switch" inside immune cells, helping them avoid complete exhaustion even during prolonged combat with cancer cells.
The effect was also confirmed in mouse glioma models. CD8⁺ T cells conditioned with ATRA maintained better immune function within the tumor, and oral administration of ATRA alone also increased both the number and function of tumor-infiltrating CD8⁺ T cells. As tumor burden decreased, survival was also extended. Notably, in a model of recurrent brain tumors, anti-PD-1 immunotherapy alone showed only limited effect, but combining it with ATRA substantially improved tumor suppression and long-term survival outcomes.
In other words, if anti-PD-1 therapy releases the "brake" imposed on immune cells, ATRA keeps their "battery" from running completely dead. By combining the two approaches, the researchers propose a new combination-therapy strategy that could help overcome the limitations of existing immunotherapy.
The team also analyzed publicly available human glioblastoma datasets. In single-cell transcriptomic data from patients treated with anti-PD-1 therapy, CD8⁺ T cells from responders showed higher retinoic-acid-responsive and WNT signaling gene signatures than those from non-responders. Separately, in an immunotherapy-naïve glioblastoma cohort, patients with a higher proportion of retinoic-acid-responsive CD8⁺ T cells showed significantly better overall survival. The team noted that this study does not directly demonstrate ATRA's therapeutic efficacy in patients, and that further clinical research will be needed to confirm appropriate administration methods, dosages, and combination effects with immunotherapy drugs before it can be applied to actual brain tumor treatment.
Professor Heung Kyu Lee said, "Glioblastoma is one of the cancers most resistant to immunotherapy, because immune cells within the tumor readily become exhausted." He added that the study is meaningful for presenting a molecular mechanism by which active vitamin A signaling helps prevent the terminal exhaustion of CD8⁺ T cells while preserving their anti-cancer function. He also noted that future work validating more precise delivery methods or combination strategies could establish this as a new approach for improving the responsiveness of immunotherapy against intractable brain tumors.
The study was conducted with Dr. In Kang, a postdoctoral researcher in KAIST's Department of Biological Sciences, as first author, and Professor Heung Kyu Lee as corresponding author. Professor Jae-Byum Chang from KAIST's Department of Materials Science and Engineering, Professor Sung Ki Lee from Konyang University College of Medicine, and Professor Stephen Ahn from Seoul St. Mary's Hospital also participated in the research. The findings were published on August 26 in the international journal Signal Transduction and Targeted Therapy.
Paper title: All-trans retinoic acid suppresses CD8⁺ T-cell terminal exhaustion and potentiates anti-PD-1 therapy in glioblastoma
DOI: 10.1038/s41392-026-02852-9
This work was supported by National Research Foundation of Korea grants (RS-2023-NR077244, RS-2024-00439735, RS-2026-25509011 to H.K.L. and RS-2024-00352668 to S.A.). This study was also supported by the Samsung Science and Technology Foundation (SSTF-BA1902-05 to H.K.L.), Republic of Korea. This research was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2023-00302794 to J.B.C.).
2026.09.08 View 3921 -
KAIST Professor Jaekyung Kim Selected as One of Asia's 12 Next-Generation Scientists
KAIST (President Choongsik Bae) announced on September 4 that Professor Jaekyung Kim from the Department of Biological Sciences has been selected as a Fellow of the “2026 Asian Young Scientist Fellowship (AYSF),” a program that supports promising young scientists across Asia.
The Asian Young Scientist Fellowship (AYSF) is a privately funded research fellowship in Asia, established to support young scientists in carrying out creative and challenging research. Since selecting its first cohort of Fellows in 2023, the AYSF selects 12 early-career researchers each year across the fundamental science disciplines of life sciences, physical sciences, and mathematics and computer science. Each selected Fellow receives a total of $100,000 USD over two years to support their research.
The AYSF does more than support young scientists across individual academic disciplines —it actively encourages interdisciplinary research that transcends traditional disciplinary boundaries to open new research directions. It places particular emphasis on supporting young scientists at the critical stage of launching their careers as independent researchers, helping them develop creative ideas and pioneer new areas of research.
Candidates are nominated from among full-time researchers at universities or research institutions in Asia who are within 10 years of completing their terminal degree (Ph.D./M.D.). Among the nominated candidates, a Selection Committee composed of scientists from Asia and around the world conducts a comprehensive evaluation of each candidate’s research achievements and future research potential.
This year, 12 early-career researchers in Asia were selected as 2026 Fellows Professor Kim was named a Fellow in the life sciences category, alongside Professor Mikyung Shin of Sungkyunkwan University, making them the two Fellows affiliated with Korean universities. Previous AYS Fellows from Korea include Professor Kyeongsu Choi of the Korea Institute for Advanced Study (KIAS) in 2023; Professor Jiheong Kang of Seoul National University in 2024; and Professor Seongjun Park of Seoul National University and Professor In-Jee Jeong of KIAS in 2025.
Professor Kim studies how the brain organizes experiences and information into memories during sleep. Using a systems- and computational-neuroscience approach, he focuses on memory consolidation—the process by which information learned during the day becomes stabilized into long-term memory during sleep—and the neural mechanisms involved. He also analyzes biological signals related to dreaming and investigates how sleep affects higher cognitive functions such as creative thinking.
Professor Kim received his bachelor's degree from Hanyang University and his Ph.D. from KAIST, and completed postdoctoral research at the University of California, San Francisco (UCSF) and the San Francisco VA Medical Center. He joined the KAIST Department of Biological Sciences in 2023 and currently leads the Neural Processing Lab.
The 2026 AYS Fellows will attend the 2026 AYSF Annual Conference on November 9, 2026, at the University of Hong Kong to showcase their research work and innovative ideas.
2026.09.04 View 2840 -
KAIST Develops a Way to Combat Cancer Cachexia, the Wasting Syndrome That Debilitates Patients
A new path has opened toward stopping cancer-associated cachexia, a devastating complication that gradually wastes patients away. A KAIST research team has developed an RNA-based therapeutic strategy that blocks a brain signal to prevent muscle loss and extend survival.
KAIST (President Choongsik Bae) announced on the 2nd of August that a joint research team led by Professor Minho Shong and Professor Jinkuk Kim from the Graduate School of Medical Science and Engineering, together with the KAIST faculty startup THOR Therapeutics (CEO Minho Shong), identified a new therapeutic principle for cancer cachexia.
Cancer cachexia affects 50 to 80 percent of all cancer patients, making it one of the most common complications of the disease. As cancer cells disrupt the body's metabolism, patients continue to lose weight and muscle mass even when eating sufficiently, leading to severe physical decline. This is a major reason chemotherapy often becomes less effective and treatment is discontinued, ultimately lowering survival rates. Existing drugs, however, have been limited to temporarily boosting appetite and have failed to fundamentally address the underlying muscle loss and metabolic dysfunction.
The research team focused on the idea that the root cause of cancer cachexia lies not in the body, but in the brain. The team noted that when GDF15 (Growth Differentiation Factor 15)—a signaling protein secreted in large amounts as cancer progresses—binds to GFRAL, a receptor protein in the brainstem, it triggers a signal instructing the body to stop eating and instead break down stored muscle and fat, driving progressive physical decline.
To block this process, the team worked with Professor Kim's group to develop a therapeutic using antisense oligonucleotides (ASO)—an RNA-based gene therapy technologies that selectively suppresses the activity of a specific gene—to prevent GFRAL from being produced in the first place.
In effect, the treatment switches off the receiver of the signal that cancer cells send instructing the body to waste away. By blocking GFRAL production at the RNA stage—the intermediate step in which genetic information is converted into protein—the therapy shuts down the cachexia-inducing signal at its source.
The team administered the treatment to mice in which cancer cachexia had already progressed. The result was a substantial reduction in muscle and fat loss, along with the restoration of the metabolic function that had previously broken down. Notably, even though treatment began after the disease had advanced significantly, survival at the study's endpoint (around day 50) was markedly higher in the treated group—90 percent—compared with just 20 percent in the untreated group, demonstrating the therapy's potential for treating cancer cachexia.
Unlike existing treatments that only stimulate appetite, this study is significant in that it blocks the underlying signal driving the wasting process itself. The therapy improved both muscle loss and metabolic dysfunction, and researchers expect that it could eventually be used alongside existing cancer treatments as a next-generation adjuvant therapy to improve patients' quality of life, treatment effectiveness, and survival rates.
"While existing therapies have only temporarily boosted appetite, this study is significant in that it directly targeted a key receptor in the brainstem at the RNA level to suppress the root cause of cancer cachexia," said Professor Song. He added that the team's goal is to move forward with follow-up preclinical research and drug manufacturing as well as quality-control systems without delay, begin clinical development in cancer patients by 2030, and develop the therapy into a treatment that improves patients' quality of life and survival rates.
Dr. Hyunjung Hong from the Graduate School of Medical Science and Engineering, Dr. Minhee Lee from THOR Therapeutics, and Dr. Minsung Park from the Graduate School of Medical Science and Engineering participated as co-first authors, with Professor Song and Professor Kim serving as co-corresponding authors. The findings were published in the international journal Cell Reports Medicine on July 27.
Paper title: Therapeutic Gfral silencing via antisense oligonucleotides ameliorates cancer-associated cachexia and extends survival in tumor-bearing mice
DOI : https://doi.org/10.1016/j.xcrm.2026.102939
This research was supported by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of SMEs and Startups.
2026.08.03 View 2122 -
KAIST Gives Antibodies “Eyes” to Detect Cancer, Targeting Cancer Mutations Inside Cells
Antibodies are like “guided missiles” that find and attack cancer cells, but cancer-causing mutations inside cells have remained a “blind spot” for treatment because antibodies cannot reach them. KAIST researchers have now succeeded in precisely targeting even intracellular cancer mutations using a newly designed antibody created through computational methods. This achievement is expected to open a new path toward next-generation precision therapies for difficult-to-treat cancers, going beyond the limitations of conventional antibody treatments.
KAIST (President Choongsik Bae) announced on the 24th of July that a research team led by Professor Byung-Ha Oh from the Department of Biological Sciences, together with researchers from Therazyne, a KAIST faculty startup specializing in protein design and headed by Professor Oh, has developed an antibody that selectively recognizes only cancer cells carrying KRAS(G12D), a representative cancer-driving mutation. By combining computational antibody design with experimental validation, the team designed a new antibody that would have been difficult to develop through conventional approaches and is now verifying its efficacy in animal disease models.
KRAS(G12D) is a mutated form of the KRAS protein, which regulates cell growth and proliferation. It is one of the most common cancer-driving mutations found in pancreatic, colorectal, and lung cancers. However, because the KRAS protein exists inside cells, it has long been considered an “undruggable target” that is difficult to directly target with conventional antibody therapeutics.
The research team focused on the natural process by which cells break down aged or damaged proteins into small fragments. The KRAS(G12D) protein inside cells is also processed in this way into small protein fragments, known as neoantigens, which serve as clues that allow immune cells to distinguish cancer cells. Some of these fragments are then transported to the cell surface and presented to immune cells. By combining computational protein design with experimental screening, the team developed a TCR-like antibody that precisely recognizes only this cancer-mutation-derived fragment.
TCR, or T cell receptor, acts as a “sensor” that allows T cells, the body’s immune cells, to read protein fragments displayed on the surface of cells and identify cancer cells or virus-infected cells. The TCR-like antibody developed in this study works on a similar principle, effectively giving an antibody the “eyes” of a T cell. It was designed to selectively recognize traces of intracellular cancer mutations that conventional antibodies cannot easily access.
Experimental results confirmed that the antibody developed by the team selectively recognizes only cancer cells carrying the KRAS(G12D) mutation, while showing little to no reaction with normal cells or other proteins. When applied to immunotherapy, it was also shown to effectively eliminate only cancer cells carrying the mutation. This finding suggests the possibility of expanding antibody therapy to intracellular cancer-driving proteins that conventional antibody treatments have been unable to target. It is also expected to serve as a platform technology for developing next-generation precision antibody therapies targeting not only KRAS but also a wide range of cancer mutations.
Professor Byung-Ha Oh said, “The antibody developed in this study can selectively identify only cancer cells carrying the KRAS(G12D) mutation, demonstrating the potential for precision antibody therapeutics that minimize damage to normal cells.” He added, “The computational antibody design technology developed in this research is expected to be widely applicable to the development of next-generation antibody therapeutics targeting KRAS as well as various other cancer mutations.”
Both the first author and corresponding authors of this study are KAIST-affiliated researchers. SangPhil Ahn, a researcher at Therazyne, participated as the first author, while Professor Byung-Ha Oh and Bo-Seong Jeong, Head of Research at Therazyne, jointly led the study as co-corresponding authors. The research was published online on June 3 in Molecular Therapy, a leading international journal in the field of gene and cell therapy.
Paper title: Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow DOI: https://doi.org/10.1016/j.ymthe.2026.05.032
This research was conducted in collaboration with Therazyne and the New Drug Development Center of the Osong Biomedical Innovation Foundation, and was supported by the Ministry of Science and ICT’s Industry-Academia-Research Linked New Drug Development Program and the National Research Foundation of Korea’s Bio & Medical Technology Development Program.
2026.07.24 View 4453 -
A Single Blood Sample May Improve the Prediction of Colorectal Cancer Recurrence and Progression, KAIST Study Finds
A single preoperative blood sample may help improve the prediction of recurrence or metastasis in patients with colorectal cancer. A joint research team from KAIST, Gangnam Severance Hospital, and Asan Medical Center has shown that, as colorectal cancer advances, the network of relationships among circulating amino acids (a kind of metabolic map) undergoes systematic remodeling. Building on this finding, the researchers developed an analytical method that showed higher predictive performance than a CEA-only model and models based solely on individual amino acid levels.
KAIST (President Choongsik Bae) announced on July 22 that a joint research team led by Professor Ji Min Lee from the Graduate School of Medical Science and Engineering and Professor Hyunwoo Kim from the Department of Chemistry, in collaboration with researchers at Gangnam Severance Hospital and Asan Medical Center, has developed a new framework for analyzing networks of circulating amino acids, which reflect the body’s metabolic state. Using this framework, the team showed that the circulating amino acid network undergoes stage-dependent remodeling that reflects systemic metabolic reprogramming. The team then used these network-derived features to develop a new analytical strategy for predicting recurrence or metastasis.
Cancer cells require large amounts of nutrients to grow and proliferate. Amino acids are not only the building blocks of proteins but also essential for energy production and DNA synthesis, making them critical to cancer cell survival and growth. Colorectal cancer, in particular, is characterized by pronounced changes in amino acid metabolism.
These changes are not confined to tumor tissue; they also appear in the bloodstream. As a result, blood amino acids have drawn attention as an important metabolic biomarker reflecting the body's overall metabolic state. Until now, however, research has focused mainly on the concentrations of individual amino acids, leaving the question of how amino acids are interconnected and change together largely unexplored.
The team used fluorine-19 nuclear magnetic resonance (¹⁹F NMR) spectroscopy to simultaneously quantify 18 circulating amino acids in a small serum sample. By analyzing not only the relative abundance of each amino acid but also the relationships among them as a network, the researchers showed that the circulating amino acid network is progressively remodeled as colorectal cancer advances.
The researchers interpreted this remodeling as evidence of systemic metabolic reprogramming (broad changes in metabolism associated with tumor progression).
As colorectal cancer progressed, the proportion of branched-chain amino acids (BCAAs) such as valine and leucine, which play key roles in muscle and energy metabolism, decreased, while the proportion of glycine and serine, which cancer cells need to synthesize DNA and proliferate rapidly, increased. This shift suggests that systemic amino acid utilization changes with advancing disease.
Glycine proved particularly notable. Although glycine is actively used by rapidly proliferating cancer cells, its relative abundance in the blood increased rather than decreased. The team also observed the emergence of a glycine-centered interaction pattern, providing further evidence of systemic metabolic remodeling during colorectal cancer progression.
The team then applied the pairwise amino acid interaction features into machine-learning models designed to identify patients with recurrence or metastasis.
In nested cross-validation, the correlation-based model showed higher predictive performance than a CEA-only model, while the combined model incorporating CEA, individual amino acid levels, and interaction-derived features achieved the highest overall performance. It also outperformed a model based solely on individual amino acid levels.
The findings suggest that examining how amino acids interact and change together, rather than considering their levels alone, provides a more informative picture of cancer progression. The study is the first to show that the interaction network among circulating amino acids could serve as a blood-based metabolic biomarker.
"We hope this will lead to new precision medicine technologies that can predict recurrence risk more accurately using a blood sample alone and help establish personalized treatment strategies," said Professor Ji Min Lee.
The research began with an interdisciplinary idea proposed through KAIST’s Master’s and PhD Venture Research Program. Graduate students in medical science and chemistry jointly conceived an interdisciplinary approach to studying cancer progression through networks of circulating amino acids. The proposal was selected for support and ultimately led to publication in the internationally renowned journal Advanced Science.
"This research embodies the spirit of KAIST by showing how students’ creative ideas and interdisciplinary collaboration can open new possibilities,” said KAIST President Choongsik Bae. He added that KAIST will continue to foster an environment in which students and researchers can freely pursue challenges across disciplinary boundaries and support creative interdisciplinary research that produces innovative technologies contributing to public health and quality of life.
The study's co-first authors are Ji-Yeon Lee, a student in the integrated master’s and doctoral program at the Graduate School of Medical Science and Engineering, and Dr. Jumi Kim, a postdoctoral researcher in the Department of Chemistry. Professors Ji Min Lee and Hyunwoo Kim of KAIST and Professor Eun Jung Park, affiliated with Gangnam Severance Hospital and Asan Medical Center, served as co-corresponding authors. The findings were published online in Advanced Science, which has a Journal Impact Factor of 14.1, on June 9, 2026.
Paper title: Circulating Amino Acid Network Remodeling Reveals Systemic Metabolic Reprogramming Predictive of Colorectal Cancer Recurrence and Metastasis
DOI: 10.1002/advs.76044
This research was supported by the Samsung Research Funding & Incubation Center of Samsung Electronics, the National Research Foundation of Korea, a Faculty Research Grant from the Department of Surgery at Asan Medical Center, and grants from the Asan Institute for Life Sciences, among others.
2026.07.22 View 3773 -
KAIST Uncovers the “Hidden Key” to Immunotherapy for Intractable Brain Tumors
Researchers have uncovered a clue to why immune checkpoint inhibitors—cancer therapies that release the immune “brakes” exploited by tumors to evade attack—show limited efficacy in some brain tumors. A KAIST research team found that B cell and antibody responses initiated in tumor-draining lymph nodes, rather than T cells alone, are critical to the antitumor effects of anti-CTLA-4 therapy, opening a new avenue for treating intractable brain tumors.
KAIST (President Choongsik Bae) announced on the 19th of July that a research team led by Professor Heung Kyu Lee from the Department of Biological Sciences has identified a previously unrecognized immune mechanism through which anti-CTLA-4, a type of immune checkpoint inhibitor, promotes B-cell responses in tumor-draining lymph nodes, thereby helping the immune system attack brain tumors.
Glioblastoma is one of the most aggressive malignant brain tumors, with frequent recurrence and a poor prognosis even after surgery and radiation therapy. Immune checkpoint inhibitors, which restore the ability of immune cells to attack cancer cells, have produced substantial therapeutic benefits in various cancers. However, their effectiveness in glioblastoma has remained limited because of the highly immunosuppressive environment surrounding the tumor.
Researchers have traditionally regarded T cells—immune cells that can directly attack cancer cells—as the primary target of immune checkpoint inhibitors. B cells, meanwhile, are well known for producing antibodies following infection or vaccination, but their role in brain tumor immunotherapy has remained largely unexplored. The research team therefore investigated whether anti-CTLA-4 could influence B-cell responses as well as T-cell responses.
The findings challenged the prevailing T-cell-centered view. In mouse glioma models, anti-CTLA-4 treatment reduced tumor burden and significantly prolonged survival. However, these therapeutic effects were largely lost in mice lacking B cells, demonstrating that B cells are required for the efficacy of anti-CTLA-4 treatment in these models.
The team also identified where B cells played their key role. Rather than being prominent in the brain, where the tumor cells were located, the response increased markedly in the Deep Cervical Lymph Nodes, which are located deep in the neck and receive lymphatic drainage from the brain. In particular, germinal center B cells and T follicular helper cells, both of which are important for antibody formation, increased together in these lymph nodes. This was accompanied by an increase in immunoglobulin G, or IgG, responses. IgG is a major class of antibody that can recognize cancer cells as targets and help immune cells eliminate them.
The resulting IgG antibodies bound to the surface of glioma cells, helping macrophages—immune cells that engulf foreign substances and cancer cells—remove the tumor cells more effectively.
The research team also examined this process directly in vivo. Using a specialized dual-reporter glioma model expressing the red fluorescent protein mCherry and the green fluorescent protein EGFP, the researchers successfully visualized tumor-infiltrating phagocytes actively engulfing glioma cells following anti-CTLA-4 treatment.
The study provides the first functional evidence that B-cell immune responses—previously known mainly for their roles in infection and vaccination—can be a key factor determining the effectiveness of immunotherapy for hard-to-treat brain tumors. It also expands the conventional T-cell-centered framework of cancer immunotherapy by showing that treatment efficacy can be strongly shaped by immune responses originating not only within the tumor, but also in tumor-draining lymph nodes outside it.
Yumin Kim, a postdoctoral researcher in the KAIST Department of Biological Sciences, served as the first author of the study, with Professor Heung Kyu Lee serving as the corresponding author. Professor Ji Eun Oh from the KAIST Graduate School of Medical Science and Engineering also contributed to the research. The findings were published on July 10 in Science Immunology.
Paper title: The efficacy of immunotherapy in glioma requires distal B-cell responses in tumor-draining lymph nodes
DOI: 10.1126/sciimmunol.adz2494
Authors: Yumin Kim, In Kang, Byeong Hoon Kang, Won Hyung Park, Chae Won Kim, Hyun-Jin Kim, Jeongwoo La, Myoung Seung Kwon, Sang Hee Park, Seo Hyeon Im, Hyeon Cheol Kim, Keun Bon Ku, Minji Kim, and Ji Eun Oh from KAIST, with Heung Kyu Lee from KAIST as the corresponding author.
This research was supported by National Research Foundation of Korea grants RS-2023-NR077244 (to H.K.L.), RS-2024-00439735 (to H.K.L.), RS-2024-00411928 (to Y.K.), RS-2025-00517107 (to J.E.O.), and RS-2026-25509011 (to H.K.L.). This study was also supported by Samsung Science and Technology Foundation grants SSTF-BA1902-05 (to H.K.L.) and SSTF-BA2201-11 (to J.E.O.).
2026.07.20 View 5468 -
KAIST Enables DNA Synthesis Using Only Temperature Instead of Chemical Reagents
"Complex chemical processes are essential for making DNA." This long-held assumption in the field of biotechnology has been overturned by a Korean research team. A KAIST research team has developed the world's first foundational technology that enables the synthesis of desired DNA using only temperature. Using this technology, the team also demonstrated a "DNA temperature black box" that records temperature changes during shipping without electricity.
KAIST announced on the 7th of July that a research team led by Professor Yeongjae Choi of the Graduate School of Engineering Biology, in collaboration with ATG Lifetech Inc. (CEO Taehoon Ryu) and a research team led by Professor Hansol Choi from the Department of Life Science at Ewha Womans University, has developed this platform technology that synthesizes desired DNA sequences by controlling only temperature.
DNA is the "blueprint" that contains the genetic information of humans and all other living organisms. Scientists use custom-made DNA in various biotechnology applications, such as diagnosing diseases, developing new drugs, and creating microorganisms with new functions. Until now, however, each time one of the four bases that make up DNA—A, T, G, and C—was connected, chemical reagents had to be added and washed out repeatedly. As a result, costly automated DNA synthesis equipment and specialized research facilities were essential.
To overcome these limitations, the research team developed "hairpin DNA that reacts only at specific temperatures." This hairpin DNA is a special DNA structure that remains folded like a hairpin and unfolds only at a certain temperature. The team placed multiple types of hairpin DNA that operate at different temperatures into a single test tube and succeeded in synthesizing desired DNA step by step by changing only the temperature in the sequence.
This opens the way for synthesizing DNA with only a general temperature control device, without the need for complex reagent replacement or large-scale equipment.
As the technology advances, it is expected to greatly reduce the cost and time required to make DNA, lowering the entry barriers not only for synthetic biology and genetic research, but also for various bioindustries such as drug development and precision medicine.
To demonstrate the practical applicability of the technology, the research team also implemented a power-free "DNA temperature black box." This device is normally stored in a freeze-dried state and begins operating when a single drop of water is added just before use. It then automatically records—directly into a DNA sequence—when, how long, and in what order the temperature changes during shipping. In addition, when exposed to temperatures above a certain level, the device changes color, allowing abnormalities to be checked visually on the spot. It is expected to be used for the quality control of products for which cold-chain distribution is important, such as vaccines, biopharmaceuticals, cell therapies, and fresh foods.
KAIST researcher Jangho Choi and GIST doctoral student Jinho Kim participated in this research as co-first authors, and the research results were published in the international journal Nature Communications on July 2.
※ Paper title: Programmable one-pot polymerase-mediated DNA synthesis via temperature control
※ DOI: https://doi.org/10.1038/s41467-026-74890-4
※ Related Video: https://drive.google.com/file/d/1bUtzC83qIm1k-hNFKTb09yFPhfsD4iU-/view?usp=drive_lin
※ Authors: Jangho Choi (KAIST, co-first author), Jinho Kim (GIST, co-first author), Hansol Choi (Ewha Womans University, corresponding author), Yeongjae Choi (KAIST, corresponding author)
This research was supported by the Ministry of Science and ICT through the Future Promising Convergence Technology Pioneer Program, the Biofoundry-Based Technology Development Program, the Young Researcher Program, and the Global Basic Research Laboratory Program.
2026.07.07 View 5207