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KAIST Develops Retinal Therapy to Restore Lost Vision
Vision is one of the most crucial human senses, yet over 300 million people worldwide are at risk of vision loss due to various retinal diseases. While recent advancements in retinal disease treatments have successfully slowed disease progression, no effective therapy has been developed to restore already lost vision—until now. KAIST researchers have successfully developed a novel drug to restore vision. < Photo 1. (From left) Ph.D. candidate Museong Kim, Professor Jin Woo Kim, and Dr. Eun Jung Lee of KAIST Department of Biological Sciences > KAIST (represented by President Kwang Hyung Lee) announced on the 30th of March that a research team led by Professor Jin Woo Kim from the Department of Biological Sciences has developed a treatment method that restores vision through retinal nerve regeneration. The research team successfully induced retinal regeneration and vision recovery in a disease-model mouse by administering a compound that blocks the PROX1 (prospero homeobox 1) protein, which suppresses retinal regeneration. Furthermore, the effect lasted for more than six months. This study marks the first successful induction of long-term neural regeneration in mammalian retinas, offering new hope to patients with degenerative retinal diseases who previously had no treatment options. As the global population continues to age, the number of retinal disease patients is steadily increasing. However, no treatments exist to restore damaged retinas and vision. The primary reason for this is the mammalian retina's inability to regenerate once damaged. Studies on cold-blooded animals, such as fish—known for their robust retinal regeneration—have shown that retinal injuries trigger Müller glia cells to dedifferentiate into retinal progenitor cells, which then generate new neurons. However, in mammals, this process is impaired, leading to permanent retinal damage. < Figure 1. Schematic diagram of the mechanism of retinal regeneration through inhibition of PROX1 migration. PROX1 protein secreted from retinal damaged retinal neurons transfers to Müllerglia and inhibits dedifferentiation into neural progenitor cells and neural regeneration. When PROX1 is captured outside the cells by an antibody against PROX1 and its transfer to Müllerglia is interfered, dedifferentiation of Müllerglia cells and retinal regeneration processes are resumed, restoring visual function. > Through this study, the research team identified the PROX1 protein as a key inhibitor of Müller glia dedifferentiation in mammals. PROX1 is a protein found in neurons of the retina, hippocampus, and spinal cord, where it suppresses neural stem cell proliferation and promotes differentiation into neurons. The researchers discovered that PROX1 accumulates in damaged mouse retinal Müller glia, but is absent in the highly regenerative Müller glia of fish. Furthermore, they demonstrated that the PROX1 found in Müller glia is not synthesized internally but rather taken up from surrounding neurons, which fail to degrade and instead secrete the protein. Based on this finding, the team developed a method to restore Müller glia’s regenerative ability by eliminating extracellular PROX1 before it reaches these cells. < Figure 2. Retinal regeneration and visual recovery in a retinitis pigmentosa model mouse through Anti-PROX1 gene therapy. After administration of adeno-associated virus expressing PROX1 neutralizing antibodies (AAV2-Anti-PROX1) to the eyes of RP1 retinitis pigmentosa model mice with vision loss, the photoreceptor cell layer of the retina is restored (A) and vision is restored (B). > This approach involves using an antibody that binds to PROX1, developed by Celliaz Inc., a biotech startup founded by Professor Jin Woo Kim’s research lab. When administered to disease-model mouse retinas, this antibody significantly promoted neural regeneration. Additionally, when delivered, the antibody gene to the retinas of retinitis pigmentosa disease model mice, it enabled sustained retinal regeneration and vision restoration for over six months. The retinal regeneration-inducing therapy is currently being developed by Celliaz Inc. for application in various degenerative retinal diseases that currently lack effective treatments. The company aims to begin clinical trials by 2028. This study was co-authored by Dr. Eun Jung Lee of Celliaz Inc. and Museong Kim, a Ph.D. candidate at KAIST, as joint first authors. The findings were published online on March 26 in the international journal Nature Communications. (Paper Title: Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer | DOI: 10.1038/s41467-025-58290-8) Dr. Eun Jung Lee stated, "We are about completing the optimization of the PROX1-neutralizing antibody (CLZ001) and move to preclinical studies before administering it to retinal disease patients. Our goal is to provide a solution for patients at risk of blindness who currently lack proper treatment options." This research was supported by research funds from Korean National Research Foundation (NRF) and the Korea Drug Development Foundation (KDDF).
2025.03.31
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KAIST provides a comprehensive resource on microbial cell factories for sustainable chemical production
In silico analysis of five industrial microorganisms identifies optimal strains and metabolic engineering strategies for producing 235 valuable chemicals Climate change and the depletion of fossil fuels have raised the global need for sustainable chemical production. In response to these environmental challenges, microbial cell factories are gaining attention as eco-friendly platforms for producing chemicals using renewable resources, while metabolic engineering technologies to enhance these cell factories are becoming crucial tools for maximizing production efficiency. However, difficulties in selecting suitable microbial strains and optimizing complex metabolic pathways continue to pose significant obstacles to practical industrial applications. KAIST (President Kwang-Hyung Lee) announced on 27th of March that Distinguished Professor Sang Yup Lee’s research team in the Department of Chemical and Biomolecular Engineering comprehensively evaluated the production capabilities of various industrial microbial cell factories using in silico simulations and, based on these findings, identified the most suitable microbial strains for producing specific chemicals as well as optimal metabolic engineering strategies. Previously, researchers attempted to determine the best strains and efficient metabolic engineering strategies among numerous microbial candidates through extensive biological experiments and meticulous verification processes. However, this approach required substantial time and costs. Recently, the introduction of genome-scale metabolic models (GEMs), which reconstruct the metabolic networks within an organism based on its entire genome information, has enabled systematic analysis of metabolic fluxes via computer simulations. This development offers a new way to overcome limitations of conventional experimental approaches, revolutionizing both strain selection and metabolic pathway design. Accordingly, Professor Lee’s team at the Department of Chemical and Biomolecular Engineering, KAIST, evaluated the production capabilities of five representative industrial microorganisms—Escherichia coli, Saccharomyces cerevisiae, Bacillus subtilis, Corynebacterium glutamicum, and Pseudomonas putida—for 235 bio-based chemicals. Using GEMs, the researchers calculated both the maximum theoretical yields and the maximum achievable yields under industrial conditions for each chemical, thereby establishing criteria to identify the most suitable strains for each target compound. < Figure 1. Outline of the strategy for improving microbial cell factories using a genome-scale metabolic model (GEM) > The team specifically proposed strategies such as introducing heterologous enzyme reactions derived from other organisms and exchanging cofactors used by microbes to expand metabolic pathways. These strategies were shown to increase yields beyond the innate metabolic capacities of the microorganisms, resulting in higher production of industrially important chemicals such as mevalonic acid, propanol, fatty acids, and isoprenoids. Moreover, by applying a computational approach to analyze metabolic fluxes in silico, the researchers suggested strategies for improving microbial strains to maximize the production of various chemicals. They quantitatively identified the relationships between specific enzyme reactions and target chemical production, as well as the relationships between enzymes and metabolites, determining which enzyme reactions should be up- or down-regulated. Through this, the team presented strategies not only to achieve high theoretical yields but also to maximize actual production capacities. < Figure 2. Comparison of production routes and maximum yields of useful chemicals using representative industrial microorganisms > Dr. Gi Bae Kim, the first author of this paper from the KAIST BioProcess Engineering Research Center, explained, “By introducing metabolic pathways derived from other organisms and exchanging cofactors, it is possible to design new microbial cell factories that surpass existing limitations. The strategies presented in this study will play a pivotal role in making microbial-based production processes more economical and efficient.” In addition, Distinguished Professor Sang Yup Lee noted, “This research serves as a key resource in the field of systems metabolic engineering, reducing difficulties in strain selection and pathway design, and enabling more efficient development of microbial cell factories. We expect it to greatly contribute to the future development of technologies for producing various eco-friendly chemicals, such as biofuels, bioplastics, and functional food materials.” This research was conducted with the support from the Development of platform technologies of microbial cell factories for the next-generation biorefineries project and Development of advanced synthetic biology source technologies for leading the biomanufacturing industry project (Project Leader: Distinguished Professor Sang Yup Lee, KAIST) from National Research Foundation supported by the Korean Ministry of Science and ICT.
2025.03.27
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KAIST Captures Protein Reaction in Just Six Milliseconds
Understanding biomolecular processes - such as protein-protein interactions and enzyme-substrate reactions that occur on the microseconds to millisecond time scale is essential for comprehending life processes and advancing drug development. KAIST researchers have developed a method for freezing and analyzing biochemical reaction dynamics within a span of just a few milliseconds, marking a significant step forward in better understanding complex biological reactions. < Photo. (From left) Professor Jin Young Kang and Haerang Hwang of the Integrated Master's and Doctoral Program of the Department of Chemistry, along with Professor Wonhee Lee of the Department of Physics > KAIST (represented by President Kwang Hyung Lee) announced on the 24th of March that a joint research team led by Professor Jin Young Kang from the Department of Chemistry and Professor Wonhee Lee from the Department of Physics has developed a parylene-based thin-film microfluidic mixing-and-spraying device for ultra-fast biochemical reaction studies. *Parylene: A key material for microfluidic devices used to observe protein dynamics at ultra-high speeds. It can be fabricated into a few micrometer-thick films, which can be used in making a spray nozzle for microfluidic devices. This research overcomes the limitations of the existing time-resolved cryo-electron microscopy (TRCEM) method by reducing sample consumption to one-third of the conventional amount while improving the minimum time resolution—down to just six milliseconds (6 ms). TRCEM is a technique that rapidly freezes protein complexes during intermediate reaction stages under cryogenic conditions, which allows researchers to analyze their structures. This approach has gained significant attention recently for its ability to capture transient biochemical events. < Figure 1. Time-resolved cryo-EM (TRCEM) technique using microfluidic channels. In order to capture the intermediate structure of biomolecules during a biochemical reaction over time, biomolecules and reaction substrates are mixed in a microfluidic channel, and then sprayed on a grid after a certain reaction time and frozen in liquid ethane to prepare a cryo-EM sample. This can then be analyzed by cryo-EM to observe the structural changes of proteins over time. > Transient intermediate structures of protein complexes could not be captured by traditional cryo-electron microscopy due to their extremely short lifespans. Although several TRCEM techniques have been developed to address this issue, previous methods were hindered by large sample consumption and limited time resolution. To overcome these challenges, the KAIST team developed a new mixing-and-spraying device using ultra-thin parylene films. The integrated design of the device further enhanced the precision and reproducibility of experiments. < Figure 2. TRCEM grid fabrication setup using a parylene-based thin-film microfluidic device and actual appearance of the device. You can see that a thin-film parylene channel is inserted into the injection nozzle. The integration of the reaction channel and the injection nozzle allowed the residence time in the device to be reduced to at least 0.5 ms. > “This research makes TRCEM more practical and paves the way for diverse applications of the parylene thin-film device in structural biology, drug development, enzyme reaction studies, and biosensor research.” Professor Jin Young Kang explained, emphasizing the significance of the study. Professor Wonhee Lee added, “The team aims to continue this research, focusing on improvement of the technique to achieve higher time resolution with minimal sample consumption.” < Figure 3. Comparison of the spraying patterns of the parylene mixing-jet device and the conventional mixing-jet device and the filament length in the resulting RecA-ssDNA filament formation reaction. It was shown that the thin film spray nozzle structure affects the uniformity and accuracy of the final reaction time. > The research findings, with Haerang Hwang (a graduate student in the integrated master's and Ph.D. program in the Department of Chemistry) as the first author, were published online on January 28, 2025, in the international journal Advanced Functional Materials. (Paper Title: “Integrated Parylene-Based Thin-Film Microfluidic Device for Time-Resolved Cryo-Electron Microscopy”, DOI: doi.org/10.1002/adfm.202418224) This research was supported by the National Research Foundation of Korea (NRF), the Samsung Future Technology Development Program, and the CELINE consortium.
2025.03.24
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KAIST Develops World-Leading Ammonia Catalyst for Hydrogen Economy
Hydrogen production using renewable energy is a key technology for eco-friendly energy and chemical production. However, storing and transporting hydrogen remains a challenge. To address this, researchers worldwide are investigating methods to store hydrogen in the form of ammonia (NH₃), which is carbon-free and easier to liquify. A research team at KAIST has successfully developed a high-performance catalyst that enables ammonia synthesis at very low temperatures and pressures without energy loss. KAIST (represented by President Kwang Hyung Lee) announced on the 11th of March that a research team led by Professor Minkee Choi from the Department of Chemical and Biomolecular Engineering has developed an innovative catalytic system that significantly enhances ammonia production while drastically reducing energy consumption and CO₂ emissions. < (From left) Baek Ye-jun, Ph.D. candidate in the Department of Biochemical Engineering, Professor Choi Min-ki > Currently, ammonia is produced using the Haber-Bosch process, a technology over a century old that relies on iron (Fe)-based catalysts. This method requires extreme conditions—temperatures above 500°C and pressures exceeding 100 atmospheres—resulting in enormous energy consumption and contributing significantly to global CO₂ emissions. Additionally, ammonia is primarily produced in large-scale industrial plants, leading to high distribution costs. As an alternative, there is growing interest in an eco-friendly process that synthesizes ammonia using green hydrogen—produced via water electrolysis—under mild conditions (300°C, 10 atmospheres). However, developing catalysts that can achieve high ammonia productivity at such low temperatures and pressures is essential, as current technologies struggle to maintain efficiency under these conditions. The research team developed a novel catalyst by incorporating ruthenium (Ru) nanoparticles and highly basic barium oxide (BaO) particles onto a conductive carbon surface, allowing it to function like a chemical capacitor*. *Capacitor: A device that stores electrical energy by separating positive and negative charges. During ammonia synthesis, hydrogen molecules (H₂) first dissociate into hydrogen atoms (H) on the ruthenium catalyst. These hydrogen atoms are further split into protons (H⁺) and electrons (e⁻). The study revealed that the acidic protons are stored in the strongly basic BaO, while the remaining electrons are separated and stored in ruthenium and carbon. This unique chemical capacitor effect significantly enhances the ruthenium catalyst's electron density, accelerating nitrogen (N₂) dissociation—the rate-limiting step of ammonia synthesis—thereby dramatically increasing catalytic activity. Furthermore, the team discovered that optimizing the nanostructure of the carbon material further boosts the electron density of ruthenium, maximizing catalytic performance. As a result, the new catalyst demonstrated over seven times higher ammonia synthesis performance compared to state-of-the-art catalysts under mild conditions (300°C, 10 atm). < Schematic diagram showing the mechanism of ruthenium catalyst activity enhancement by barium oxide cocatalyst > Professor Minkee Choi stated, “This research has garnered significant attention for demonstrating that catalytic activity can be greatly enhanced by controlling electron transfer within a thermal catalytic reaction system, not just in electrochemical processes.” He further explained, “Our findings confirm that high-performance catalysts can enable efficient ammonia synthesis under low-temperature and low-pressure conditions. This could shift ammonia production from centralized, large-scale industrial plants to decentralized, small-scale production, making the hydrogen economy more sustainable and flexible.” The study was led by Professor Minkee Choi as corresponding author and Yaejun Baik, a Ph.D. candidate, as first author. The research findings were published in Nature Catalysis on February 24. (Paper title: “Electron and proton storage on separate Ru and BaO domains mediated by conductive low-work-function carbon to accelerate ammonia synthesis,” https://doi.org/10.1038/s41929-025-01302-z) This research was supported by the Korea Institute of Energy Research and the National Research Foundation of Korea.
2025.03.11
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KAIST develops a new, bone-like material that strengthens with use in collaboration with GIT
Materials used in apartment buildings, vehicles, and other structures deteriorate over time under repeated loads, leading to failure and breakage. A joint research team from Korea and the United States has successfully developed a bioinspired material that becomes stronger with use, taking inspiration from the way bones synthesize minerals from bodily fluids under stress, increasing bone density. < (From left) Professor Sung Hoon Kang of the Department of Materials Science and Engineering, Johns Hopkins University Ph.D. candidates Bohan Sun and Grant Kitchen, Professor Yuhang Hu and Ph.D. candidate Dongjung He of Georgia Institute of Technology > KAIST (represented by President Kwang Hyung Lee) announced on the 20th of February that a research team led by Professor Sung Hoon Kang from the Department of Materials Science and Engineering, in collaboration with Johns Hopkins University and the Georgia Institute of Technology, had developed a new material that strengthens with repeated use, similar to how bones become stronger with exercise. Professor Kang’s team sought to address the issue of conventional materials degrading with repeated use. Inspired by the biological process where stress triggers cells to form minerals that strengthen bones, the team developed a material that synthesizes minerals under stress without relying on cellular activity. This innovation is expected to enable applications in a variety of fields. To replace the function of cells, the research team created a porous piezoelectric substrate that converts mechanical force into electricity and actually generates more charge under greater force. They then synthesized a composite material by infusing it with an electrolyte containing mineral components similar to those in blood. < Figure 1. Schematic diagram of the biomimetic concept based on bone and pitcher plants, the reversible strengthening mechanism, the process of fabricating porous composites, the mechanical property changes with increasing stiffness and energy dissipation after cyclic loading, and the reprogrammable self-folding mechanism and applications > After subjecting the material to periodic forces and measuring changes in its properties, they observed that its stiffness increased proportionally with the frequency and magnitude of stress and that its energy dissipation capability improved. The reason for such properties was found to be due to minerals forming inside the porous material under repeated stress, as observed through micro-CT imaging of its internal structure. When subjected to large forces, these minerals fractured and dissipated energy, only to reform under further cyclic stress. Unlike conventional materials that weaken with repeated use, this new material simultaneously enhances stiffness and impact absorption over time. < Figure 2. Comparison of the changes in properties of the newly developed new material (LIPPS) with other materials under cyclic loading. (A) Graph showing the relative change rate of energy dissipation after cyclic loading and the relative change rate of elastic modulus upon unloading. LIPPS is in a new area that existing materials have not reached, and shows the characteristics of simultaneous increases in elastic modulus and energy dissipation. (B) Graph comparing the performance of LIPPS with current state-of-the-art mechanically adaptive materials. (Left) The maximum property change rate compared to the baseline after cyclic loading, LIPPS shows much higher changes in elastic modulus, dissipated energy density and ratio, toughness (impact resistance), and stored energy density than the existing adaptive materials. (Right) The absolute value range of the reported properties before and after cyclic loading shows that LIPPS has higher elastic modulus and toughness than the existing adaptive materials. > Moreover, because its properties improve in proportion to the magnitude and frequency of applied stress, it can self-adjust to achieve mechanical property distributions suitable for different structural applications. It also possesses self-healing capabilities. Professor Kang stated, "This newly developed material, which strengthens and absorbs impact better with repeated use compared to conventional materials, holds great potential for applications in artificial joints, as well as in aircraft, ships, automobiles, and structural engineering." This study, with Professor Sung Hoon Kang as the corresponding author, was published in Science Advances (Vol. 11, Issue 6, February). (Paper title: “A material dynamically enhancing both load-bearing and energy-dissipation capability under cyclic loading”) DOI: 10.1126/sciadv.adt3979 This research was conducted as a joint effort with Johns Hopkins University's Extreme Materials Institute and the Georgia Institute of Technology, supported by the National Research Foundation of Korea’s Brain Pool Plus program.
2025.02.22
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KAIST Research Team Develops an AI Framework Capable of Overcoming the Strength-Ductility Dilemma in Additive-manufactured Titanium Alloys
<(From Left) Ph.D. Student Jaejung Park and Professor Seungchul Lee of KAIST Department of Mechanical Engineering and , Professor Hyoung Seop Kim of POSTECH, and M.S.–Ph.D. Integrated Program Student Jeong Ah Lee of POSTECH. > The KAIST research team led by Professor Seungchul Lee from Department of Mechanical Engineering, in collaboration with Professor Hyoung Seop Kim’s team at POSTECH, successfully overcame the strength–ductility dilemma of Ti 6Al 4V alloy using artificial intelligence, enabling the production of high strength, high ductility metal products. The AI developed by the team accurately predicts mechanical properties based on various 3D printing process parameters while also providing uncertainty information, and it uses both to recommend process parameters that hold high promise for 3D printing. Among various 3D printing technologies, laser powder bed fusion is an innovative method for manufacturing Ti-6Al-4V alloy, renowned for its high strength and bio-compatibility. However, this alloy made via 3D printing has traditionally faced challenges in simultaneously achieving high strength and high ductility. Although there have been attempts to address this issue by adjusting both the printing process parameters and heat treatment conditions, the vast number of possible combinations made it difficult to explore them all through experiments and simulations alone. The active learning framework developed by the team quickly explores a wide range of 3D printing process parameters and heat treatment conditions to recommend those expected to improve both strength and ductility of the alloy. These recommendations are based on the AI model’s predictions of ultimate tensile strength and total elongation along with associated uncertainty information for each set of process parameters and heat treatment conditions. The recommended conditions are then validated by performing 3D printing and tensile tests to obtain the true mechanical property values. These new data are incorporated into further AI model training, and through iterative exploration, the optimal process parameters and heat treatment conditions for producing high-performance alloys were determined in only five iterations. With these optimized conditions, the 3D printed Ti-6Al-4V alloy achieved an ultimate tensile strength of 1190 MPa and a total elongation of 16.5%, successfully overcoming the strength–ductility dilemma. Professor Seungchul Lee commented, “In this study, by optimizing the 3D printing process parameters and heat treatment conditions, we were able to develop a high-strength, high-ductility Ti-6Al-4V alloy with minimal experimentation trials. Compared to previous studies, we produced an alloy with a similar ultimate tensile strength but higher total elongation, as well as that with a similar elongation but greater ultimate tensile strength.” He added, “Furthermore, if our approach is applied not only to mechanical properties but also to other properties such as thermal conductivity and thermal expansion, we anticipate that it will enable efficient exploration of 3D printing process parameters and heat treatment conditions.” This study was published in Nature Communications on January 22 (https://doi.org/10.1038/s41467-025-56267-1), and the research was supported by the National Research Foundation of Korea’s Nano & Material Technology Development Program and the Leading Research Center Program.
2025.02.21
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KAIST Discovers Molecular Switch that Reverses Cancerous Transformation at the Critical Moment of Transition
< (From left) PhD student Seoyoon D. Jeong, (bottom) Professor Kwang-Hyun Cho, (top) Dr. Dongkwan Shin, Dr. Jeong-Ryeol Gong > Professor Kwang-Hyun Cho’s research team has recently been highlighted for their work on developing an original technology for cancer reversal treatment that does not kill cancer cells but only changes their characteristics to reverse them to a state similar to normal cells. This time, they have succeeded in revealing for the first time that a molecular switch that can induce cancer reversal at the moment when normal cells change into cancer cells is hidden in the genetic network. KAIST (President Kwang-Hyung Lee) announced on the 5th of February that Professor Kwang-Hyun Cho's research team of the Department of Bio and Brain Engineering has succeeded in developing a fundamental technology to capture the critical transition phenomenon at the moment when normal cells change into cancer cells and analyze it to discover a molecular switch that can revert cancer cells back into normal cells. A critical transition is a phenomenon in which a sudden change in state occurs at a specific point in time, like water changing into steam at 100℃. This critical transition phenomenon also occurs in the process in which normal cells change into cancer cells at a specific point in time due to the accumulation of genetic and epigenetic changes. The research team discovered that normal cells can enter an unstable critical transition state where normal cells and cancer cells coexist just before they change into cancer cells during tumorigenesis, the production or development of tumors, and analyzed this critical transition state using a systems biology method to develop a cancer reversal molecular switch identification technology that can reverse the cancerization process. They then applied this to colon cancer cells and confirmed through molecular cell experiments that cancer cells can recover the characteristics of normal cells. This is an original technology that automatically infers a computer model of the genetic network that controls the critical transition of cancer development from single-cell RNA sequencing data, and systematically finds molecular switches for cancer reversion by simulation analysis. It is expected that this technology will be applied to the development of reversion therapies for other cancers in the future. Professor Kwang-Hyun Cho said, "We have discovered a molecular switch that can revert the fate of cancer cells back to a normal state by capturing the moment of critical transition right before normal cells are changed into an irreversible cancerous state." < Figure 1. Overall conceptual framework of the technology that automatically constructs a molecular regulatory network from single-cell RNA sequencing data of colon cancer cells to discover molecular switches for cancer reversion through computer simulation analysis. Professor Kwang-Hyun Cho's research team established a fundamental technology for automatic construction of a computer model of a core gene network by analyzing the entire process of tumorigenesis of colon cells turning into cancer cells, and developed an original technology for discovering the molecular switches that can induce cancer cell reversal through attractor landscape analysis. > He continued, "In particular, this study has revealed in detail, at the genetic network level, what changes occur within cells behind the process of cancer development, which has been considered a mystery until now." He emphasized, "This is the first study to reveal that an important clue that can revert the fate of tumorigenesis is hidden at this very critical moment of change." < Figure 2. Identification of tumor transition state using single-cell RNA sequencing data from colorectal cancer. Using single-cell RNA sequencing data from colorectal cancer patient-derived organoids for normal and cancerous tissues, a critical transition was identified in which normal and cancerous cells coexist and instability increases (a-d). The critical transition was confirmed to show intermediate levels of major phenotypic features related to cancer or normal tissues that are indicative of the states between the normal and cancerous cells (e). > The results of this study, conducted by KAIST Dr. Dongkwan Shin (currently at the National Cancer Center), Dr. Jeong-Ryeol Gong, and doctoral student Seoyoon D. Jeong jointly with a research team at Seoul National University that provided the organoids (in vitro cultured tissues) from colon cancer patient, were published as an online paper in the international journal ‘Advanced Science’ published by Wiley on January 22nd. (Paper title: Attractor landscape analysis reveals a reversion switch in the transition of colorectal tumorigenesis) (DOI: https://doi.org/10.1002/advs.202412503) < Figure 3. Reconstruction of a dynamic network model for the transition state of colorectal cancer. A new technology was established to build a gene network computer model that can simulate the dynamic changes between genes by integrating single-cell RNA sequencing data and existing experimental results on gene-to-gene interactions in the critical transition of cancer. (a). Using this technology, a gene network computer model for the critical transition of colorectal cancer was constructed, and the distribution of attractors representing normal and cancer cell phenotypes was investigated through attractor landscape analysis (b-e). > This study was conducted with the support of the National Research Foundation of Korea under the Ministry of Science and ICT through the Mid-Career Researcher Program and Basic Research Laboratory Program and the Disease-Centered Translational Research Project of the Korea Health Industry Development Institute (KHIDI) of the Ministry of Health and Welfare. < Figure 4. Quantification of attractor landscapes and discovery of transcription factors for cancer reversibility through perturbation simulation analysis. A methodology for implementing discontinuous attractor landscapes continuously from a computer model of gene networks and quantifying them as cancer scores was introduced (a), and attractor landscapes for the critical transition of colorectal cancer were secured (b-d). By tracking the change patterns of normal and cancer cell attractors through perturbation simulation analysis for each gene, the optimal combination of transcription factors for cancer reversion was discovered (e-h). This was confirmed in various parameter combinations as well (i). > < Figure 5. Identification and experimental validation of the optimal target gene for cancer reversion. Among the common target genes of the discovered transcription factor combinations, we identified cancer reversing molecular switches that are predicted to suppress cancer cell proliferation and restore the characteristics of normal colon cells (a-d). When inhibitors for the molecular switches were treated to organoids derived from colon cancer patients, it was confirmed that cancer cell proliferation was suppressed and the expression of key genes related to cancer development was inhibited (e-h), and a group of genes related to normal colon epithelium was activated and transformed into a state similar to normal colon cells (i-j). > < Figure 6. Schematic diagram of the research results. Professor Kwang-Hyun Cho's research team developed an original technology to systematically discover key molecular switches that can induce reversion of colon cancer cells through a systems biology approach using an attractor landscape analysis of a genetic network model for the critical transition at the moment of transformation from normal cells to cancer cells, and verified the reversing effect of actual colon cancer through cellular experiments. >
2025.02.05
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KAIST Uncovers the Principles of Gene Expression Regulation in Cancer and Cellular Functions
< (From left) Professor Seyun Kim, Professor Gwangrog Lee, Dr. Hyoungjoon Ahn, Dr. Jeongmin Yu, Professor Won-Ki Cho, and (below) PhD candidate Kwangmin Ryu of the Department of Biological Sciences> A research team at KAIST has identified the core gene expression networks regulated by key proteins that fundamentally drive phenomena such as cancer development, metastasis, tissue differentiation from stem cells, and neural activation processes. This discovery lays the foundation for developing innovative therapeutic technologies. On the 22nd of January, KAIST (represented by President Kwang Hyung Lee) announced that the joint research team led by Professors Seyun Kim, Gwangrog Lee, and Won-Ki Cho from the Department of Biological Sciences had uncovered essential mechanisms controlling gene expression in animal cells. Inositol phosphate metabolites produced by inositol metabolism enzymes serve as vital secondary messengers in eukaryotic cell signaling systems and are broadly implicated in cancer, obesity, diabetes, and neurological disorders. The research team demonstrated that the inositol polyphosphate multikinase (IPMK) enzyme, a key player in the inositol metabolism system, acts as a critical transcriptional activator within the core gene expression networks of animal cells. Notably, although IPMK was previously reported to play an important role in the transcription process governed by serum response factor (SRF), a representative transcription factor in animal cells, the precise mechanism of its action was unclear. SRF is a transcription factor directly controlling the expression of at least 200–300 genes, regulating cell growth, proliferation, apoptosis, and motility, and is indispensable for organ development, such as in the heart. The team discovered that IPMK binds directly to SRF, altering the three-dimensional structure of the SRF protein. This interaction facilitates the transcriptional activity of various genes through the SRF activated by IPMK, demonstrating that IPMK acts as a critical regulatory switch to enhance SRF's protein activity. < Figure 1. The serum response factor (SRF) protein, a key transcription factor in animal cells, directly binds to inositol polyphosphate multikinase (IPMK) enzyme and undergoes structural change to acquire DNA binding ability, and precisely regulates growth and differentiation of animal cells through transcriptional activation. > The team further verified that disruptions in the direct interaction between IPMK and SRF lead to the reduced functionality and activity of SRF, causing severe impairments in gene expression. By highlighting the significance of the intrinsically disordered region (IDR) in SRF, the researchers underscored the biological importance of intrinsically disordered proteins (IDPs). Unlike most proteins that adopt distinct structures through folding, IDPs, including those with IDRs, do not exhibit specific structures but play crucial biological roles, attracting significant attention in the scientific community. Professor Seyun Kim commented, "This study provides a vital mechanism proving that IPMK, a key enzyme in the inositol metabolism system, is a major transcriptional activator in the core gene expression network of animal cells. By understanding fundamental processes such as cancer development and metastasis, tissue differentiation from stem cells, and neural activation through SRF, we hope this discovery will lead to the broad application of innovative therapeutic technologies." The findings were published on January 7th in the international journal Nucleic Acids Research (IF=16.7, top 1.8% in Biochemistry and Molecular Biology), under the title “Single-molecule analysis reveals that IPMK enhances the DNA-binding activity of the transcription factor SRF" (DOI: 10.1093/nar/gkae1281). This research was supported by the National Research Foundation of Korea's Mid-career Research Program, Leading Research Center Program, and Global Research Laboratory Program, as well as by the Suh Kyungbae Science Foundation and the Samsung Future Technology Development Program.
2025.01.24
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A Way for Smartwatches to Detect Depression Risks Devised by KAIST and U of Michigan Researchers
- A international joint research team of KAIST and the University of Michigan developed a digital biomarker for predicting symptoms of depression based on data collected by smartwatches - It has the potential to be used as a medical technology to replace the economically burdensome fMRI measurement test - It is expected to expand the scope of digital health data analysis The CORONA virus pandemic also brought about a pandemic of mental illness. Approximately one billion people worldwide suffer from various psychiatric conditions. Korea is one of more serious cases, with approximately 1.8 million patients exhibiting depression and anxiety disorders, and the total number of patients with clinical mental diseases has increased by 37% in five years to approximately 4.65 million. A joint research team from Korea and the US has developed a technology that uses biometric data collected through wearable devices to predict tomorrow's mood and, further, to predict the possibility of developing symptoms of depression. < Figure 1. Schematic diagram of the research results. Based on the biometric data collected by a smartwatch, a mathematical algorithm that solves the inverse problem to estimate the brain's circadian phase and sleep stages has been developed. This algorithm can estimate the degrees of circadian disruption, and these estimates can be used as the digital biomarkers to predict depression risks. > KAIST (President Kwang Hyung Lee) announced on the 15th of January that the research team under Professor Dae Wook Kim from the Department of Brain and Cognitive Sciences and the team under Professor Daniel B. Forger from the Department of Mathematics at the University of Michigan in the United States have developed a technology to predict symptoms of depression such as sleep disorders, depression, loss of appetite, overeating, and decreased concentration in shift workers from the activity and heart rate data collected from smartwatches. According to WHO, a promising new treatment direction for mental illness focuses on the sleep and circadian timekeeping system located in the hypothalamus of the brain, which directly affect impulsivity, emotional responses, decision-making, and overall mood. However, in order to measure endogenous circadian rhythms and sleep states, blood or saliva must be drawn every 30 minutes throughout the night to measure changes in the concentration of the melatonin hormone in our bodies and polysomnography (PSG) must be performed. As such treatments requires hospitalization and most psychiatric patients only visit for outpatient treatment, there has been no significant progress in developing treatment methods that take these two factors into account. In addition, the cost of the PSG test, which is approximately $1000, leaves mental health treatment considering sleep and circadian rhythms out of reach for the socially disadvantaged. The solution to overcome these problems is to employ wearable devices for the easier collection of biometric data such as heart rate, body temperature, and activity level in real time without spatial constraints. However, current wearable devices have the limitation of providing only indirect information on biomarkers required by medical staff, such as the phase of the circadian clock. The joint research team developed a filtering technology that accurately estimates the phase of the circadian clock, which changes daily, such as heart rate and activity time series data collected from a smartwatch. This is an implementation of a digital twin that precisely describes the circadian rhythm in the brain, and it can be used to estimate circadian rhythm disruption. < Figure 2. The suprachiasmatic nucleus located in the hypothalamus of the brain is the central biological clock that regulates the 24-hour physiological rhythm and plays a key role in maintaining the body’s circadian rhythm. If the phase of this biological clock is disrupted, it affects various parts of the brain, which can cause psychiatric conditions such as depression. > The possibility of using the digital twin of this circadian clock to predict the symptoms of depression was verified through collaboration with the research team of Professor Srijan Sen of the Michigan Neuroscience Institute and Professor Amy Bohnert of the Department of Psychiatry of the University of Michigan. The collaborative research team conducted a large-scale prospective cohort study involving approximately 800 shift workers and showed that the circadian rhythm disruption digital biomarker estimated through the technology can predict tomorrow's mood as well as six symptoms, including sleep problems, appetite changes, decreased concentration, and suicidal thoughts, which are representative symptoms of depression. < Figure 3. The circadian rhythm of hormones such as melatonin regulates various physiological functions and behaviors such as heart rate and activity level. These physiological and behavioral signals can be measured in daily life through wearable devices. In order to estimate the body’s circadian rhythm inversely based on the measured biometric signals, a mathematical algorithm is needed. This algorithm plays a key role in accurately identifying the characteristics of circadian rhythms by extracting hidden physiological patterns from biosignals. > Professor Dae Wook Kim said, "It is very meaningful to be able to conduct research that provides a clue for ways to apply wearable biometric data using mathematics that have not previously been utilized for actual disease management." He added, "We expect that this research will be able to present continuous and non-invasive mental health monitoring technology. This is expected to present a new paradigm for mental health care. By resolving some of the major problems socially disadvantaged people may face in current treatment practices, they may be able to take more active steps when experiencing symptoms of depression, such as seeking counsel before things get out of hand." < Figure 4. A mathematical algorithm was devised to circumvent the problems of estimating the phase of the brain's biological clock and sleep stages inversely from the biodata collected by a smartwatch. This algorithm can estimate the degree of daily circadian rhythm disruption, and this estimate can be used as a digital biomarker to predict depression symptoms. > The results of this study, in which Professor Dae Wook Kim of the Department of Brain and Cognitive Sciences at KAIST participated as the joint first author and corresponding author, were published in the online version of the international academic journal npj Digital Medicine on December 5, 2024. (Paper title: The real-world association between digital markers of circadian disruption and mental health risks) DOI: 10.1038/s41746-024-01348-6 This study was conducted with the support of the KAIST's Research Support Program for New Faculty Members, the US National Science Foundation, the US National Institutes of Health, and the US Army Research Institute MURI Program.
2025.01.20
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KAIST Develops Neuromorphic Semiconductor Chip that Learns and Corrects Itself
< Photo. The research team of the School of Electrical Engineering posed by the newly deveoped processor. (From center to the right) Professor Young-Gyu Yoon, Integrated Master's and Doctoral Program Students Seungjae Han and Hakcheon Jeong and Professor Shinhyun Choi > - Professor Shinhyun Choi and Professor Young-Gyu Yoon’s Joint Research Team from the School of Electrical Engineering developed a computing chip that can learn, correct errors, and process AI tasks - Equipping a computing chip with high-reliability memristor devices with self-error correction functions for real-time learning and image processing Existing computer systems have separate data processing and storage devices, making them inefficient for processing complex data like AI. A KAIST research team has developed a memristor-based integrated system similar to the way our brain processes information. It is now ready for application in various devices including smart security cameras, allowing them to recognize suspicious activity immediately without having to rely on remote cloud servers, and medical devices with which it can help analyze health data in real time. KAIST (President Kwang Hyung Lee) announced on the 17th of January that the joint research team of Professor Shinhyun Choi and Professor Young-Gyu Yoon of the School of Electrical Engineering has developed a next-generation neuromorphic semiconductor-based ultra-small computing chip that can learn and correct errors on its own. < Figure 1. Scanning electron microscope (SEM) image of a computing chip equipped with a highly reliable selector-less 32×32 memristor crossbar array (left). Hardware system developed for real-time artificial intelligence implementation (right). > What is special about this computing chip is that it can learn and correct errors that occur due to non-ideal characteristics that were difficult to solve in existing neuromorphic devices. For example, when processing a video stream, the chip learns to automatically separate a moving object from the background, and it becomes better at this task over time. This self-learning ability has been proven by achieving accuracy comparable to ideal computer simulations in real-time image processing. The research team's main achievement is that it has completed a system that is both reliable and practical, beyond the development of brain-like components. The research team has developed the world's first memristor-based integrated system that can adapt to immediate environmental changes, and has presented an innovative solution that overcomes the limitations of existing technology. < Figure 2. Background and foreground separation results of an image containing non-ideal characteristics of memristor devices (left). Real-time image separation results through on-device learning using the memristor computing chip developed by our research team (right). > At the heart of this innovation is a next-generation semiconductor device called a memristor*. The variable resistance characteristics of this device can replace the role of synapses in neural networks, and by utilizing it, data storage and computation can be performed simultaneously, just like our brain cells. *Memristor: A compound word of memory and resistor, next-generation electrical device whose resistance value is determined by the amount and direction of charge that has flowed between the two terminals in the past. The research team designed a highly reliable memristor that can precisely control resistance changes and developed an efficient system that excludes complex compensation processes through self-learning. This study is significant in that it experimentally verified the commercialization possibility of a next-generation neuromorphic semiconductor-based integrated system that supports real-time learning and inference. This technology will revolutionize the way artificial intelligence is used in everyday devices, allowing AI tasks to be processed locally without relying on remote cloud servers, making them faster, more privacy-protected, and more energy-efficient. “This system is like a smart workspace where everything is within arm’s reach instead of having to go back and forth between desks and file cabinets,” explained KAIST researchers Hakcheon Jeong and Seungjae Han, who led the development of this technology. “This is similar to the way our brain processes information, where everything is processed efficiently at once at one spot.” The research was conducted with Hakcheon Jeong and Seungjae Han, the students of Integrated Master's and Doctoral Program at KAIST School of Electrical Engineering being the co-first authors, the results of which was published online in the international academic journal, Nature Electronics, on January 8, 2025. *Paper title: Self-supervised video processing with self-calibration on an analogue computing platform based on a selector-less memristor array ( https://doi.org/10.1038/s41928-024-01318-6 ) This research was supported by the Next-Generation Intelligent Semiconductor Technology Development Project, Excellent New Researcher Project and PIM AI Semiconductor Core Technology Development Project of the National Research Foundation of Korea, and the Electronics and Telecommunications Research Institute Research and Development Support Project of the Institute of Information & communications Technology Planning & Evaluation.
2025.01.17
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“Cross-Generation Collaborative Labs” for Semiconductor, Chemistry, and Computer Science Opened
< Photo of Professor Hoi-Jun Yoo (center) of the School of Electrical Engineering at the signboard unveiling ceremony > KAIST held a ceremony to mark the opening of three additional ‘Cross-Generation Collaborative Labs’ on the morning of January 7th, 2025. The “Next-Generation AI Semiconductor System Lab” by Professor Hoi-Jun Yoo of the School of Electrical Engineering, the “Molecular Spectroscopy and Chemical Dynamics Lab” by Professor Sang Kyu Kim of the Department of Chemistry, and the “Advanced Data Computing Lab” by Professor Sue Bok Moon of the School of Computer Science are the three new labs given the honored titled of the “Cross-Generation Collaborative Lab”. The Cross-Generation Collaborative Lab is KAIST’s unique system that was set up to facilitate the collaboration between retiring professors and junior professors to continue the achievements and know-how the elders have accumulated over their academic career. Since its introduction in 2018, nine labs have been named to be the Cross-Generation Labs, and this year’s new addition brings the total up to twelve. The ‘Next-Generation AI Semiconductor System Lab’ led by Professor Hoi-Jun Yoo will be operated by Professor Joo-Young Kim of the same school. Professor Hoi-Jun Yoo is a world-renowned scholar with outstanding research achievements in the field of on-device AI semiconductor design. Professor Joo-Young Kim is an up-and-coming researcher studying large language models and design of AI semiconductors for server computers, and is currently researching technologies to design PIM (Processing-in-Memory), a core technology in the field of AI semiconductors. Their research goal is to systematically collaborate and transfer next-generation AI semiconductor design technology, including brain-mimicking AI algorithms such as deep neural networks and generative AI, to integrate core technologies, and to maximize the usability of R&D outputs, thereby further solidifying the position of Korean AI semiconductor companies in the global market. Professor Hoi-Jun Yoo said, “I believe that, we will be able to present a development direction of for the next-generation AI semiconductors industries at home and abroad through collaborative research and play a key role in transferring and expanding global leadership.” < Professor Sang Kyu Kim of the Department of Chemistry (middle), at the signboard unveiling ceremony for his laboratory > The “Molecular Spectroscopy and Chemical Dynamics Laboratory”, where Professor Sang Kyu Kim of the Department of Chemistry is in charge, will be operated by Professor Tae Kyu Kim of the same department, and another professor in the field of spectroscopy and dynamics will join in the future. Professor Sang Kyu Kim has secured technologies for developing unique experimental equipment based on ultrashort lasers and supersonic molecular beams, and is a world leader who has been creatively pioneering new fields of experimental physical chemistry. The research goal is to describe chemical reactions and verify from a quantum mechanical perspective and introduce new theories and technologies to pursue a complete understanding of the principles of chemical reactions. In addition, the accompanying basic scientific knowledge will be applied to the design of new materials. Professor Sang Kyu Kim said, “I am very happy to be able to pass on the research infrastructure to the next generation through this system, and I will continue to nurture it to grow into a world-class research lab through trans-generational collaborative research.” < Photo of Professor Sue Bok Moon (center) at the signboard unveiling ceremony by the School of Computing > Lastly, the “Advanced Data Computing Lab” led by Professor Sue Bok Moon is joined by Professor Mee Young Cha of the same school and Professor Wonjae Lee of the Graduate School of Culture Technology. Professor Sue Bok Moon showed the infinite possibilities of large-scale data-based social network research through Cyworld, YouTube, and Twitter, and had a great influence on related fields beyond the field of computer science. Professor Mee Young Cha is a data scientist who analyzes difficult social issues such as misinformation, poverty, and disaster detection using big data-based AI. She is the first Korean to be recognized for her achievements as the director of the Max Planck Institute in Germany, a world-class basic science research institute. Therefore, there is high expectation for synergy effects from overseas collaborative research and technology transfer and sharing among the participating professors of the collaborative research lab. Professor Wonjae Lee is researching dynamic interaction analysis between science and technology using structural topic models. They plan to conduct research aimed at improving the analysis and understanding of negative influences occurring online, and in particular, developing a hateful precursor detection model using emotions and morality to preemptively block hateful expressions. Professor Sue Bok Moon said, “Through this collaborative research lab, we will play a key role in conducting in-depth collaborative research on unexpected negative influences in the AI era so that we can have a high level of competitiveness worldwide.” The ceremonies for the unveiling of the new Cross-Generation Collaborative Lab signboard were held in front of each lab from 10:00 AM on the 7th, in the attendance of President Kwang Hyung Lee, Senior Vice President for Research Sang Yup Lee, and other key officials of KAIST and the new staff members to join the laboratories.
2025.01.07
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KAIST develops ‘Hoverbike’ to roam the future skies
< Photo 1. A group photo of the research team > Hoverbike is a kind of next-generation mobility that can complement the existing transportation system and can be used as an air transportation means without traffic congestion through high-weight payloads and long-distance flights. It is expected that domestic researchers will contribute to the development of the domestic PAV* and UAM markets by developing a domestically developed manned/unmanned hybrid aircraft that escapes dependence on foreign technology through the development of a high-performance hoverbike. *PAV: Personal Aerial Vehicle. It is a key element of future urban air mobility (UAM, Urban Air Mobility) and constitutes an important part of the next-generation transportation system. KAIST (President Kwang-Hyung Lee) announced on the 27th of December that the research team of Professor Hyochoong Bang of the Department of Aerospace Engineering successfully developed the core technology of a highly reliable multipurpose vertical takeoff and landing hoverbike that can be operated by both manned and unmanned vehicles. This research was participated by the research teams of Professor Jae-Hung Han, Professor Ji-yun Lee, Professor Jae-myung Ahn, Professor Han-Lim Choi, and Professor Chang-Hun Lee of the Department of Aerospace Engineering at KAIST, Professor Dongjin Lee of the Department of Unmanned Aerial Vehicles at Hanseo University, and Professor Jong-Oh Park of the Department of Electronics Engineering at Dong-A University. The research team secured key technologies related to the optimal design of a multipurpose aircraft, hybrid propulsion system, highly reliable precision navigation and flight control system, autonomous flight, and fault detection for the development of a high-performance hoverbike. < Figure 1. Key features of high-reliability multi-purpose hoverbike > The hoverbike platform introduced a gasoline engine-based hybrid system to overcome the shortcomings of battery-based drones, achieving approximately 60% better performance and maximum payload weight compared to overseas technology levels. Through this, it is expected to be utilized in various fields such as emergency supply delivery, logistics, and rescue activities for civilian use, and military transport and mission support for military use. The navigation system was applied by implementing multi-sensor fusion technology based on DGPS/INS* to enable stable flight even in environments without GPS or with weak signals using high-reliability precision navigation technology. *DGPS/INS: Navigation solution combining high accuracy of Differential GPS (DGPS) and Inertial Navigation System (INS) In addition, high-reliability flight control technology was developed to enable reliable maneuvering even under external factors such as payload and wind, and model uncertainty, and fault detection technology was also developed. A guidance technique to automatically land on a helipad after selecting a safe automatic landing area by configuring a high-reliability autonomous flight system was implemented with high accuracy. Stable operation is possible even in complex environments through obstacle avoidance and automatic landing autonomous flight technology. < Figure 2. Hoverbike prototype model > Professor Hyochoong Bang, the research director, emphasized, “We have proven the high practicality of the hoverbike in various environments through high-reliability flight control and precision navigation technology.” He added, “The hoverbike is a promising research result that can not only provide a major path leading to PAVs and future aircraft, but also surpass existing drone technology by several levels. This achievement is even more meaningful because it is the result of five years of effort by eight joint research teams, including the project’s practitioners, PhD students Kwangwoo Jang and Hyungjoo Ahn.” This study aims to secure core technologies for manned/unmanned multipurpose hoverbikes that can be utilized as new concept aircraft in the defense and civilian sectors. It started as the Defense Acquisition Program Administration’s Defense Technology for Future Challenge Research and Development Project in 2019 and was completed in 2024 under the management of the Agency for Defense Development. It is scheduled to be exhibited for the first time at the 2025 Drone Show Korea (DSK2025), which will be held at BEXCO in Busan from February 26 to 28, 2025.
2024.12.27
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