NT
-
Editing Parkinson's Disease – KAIST Makes World's First Discovery of an Inflammatory RNA Editing Enzyme
< Professor Minee Choi of the Department of Brain and Cognitive Sciences (top left). Professor Sonia Gandhi (top right) and Professor Klenerman of the University College London (bottom right) >
Parkinson's disease (PD) is a neurodegenerative disorder in which the α-synuclein protein abnormally aggregates within brain cells, causing neuronal damage. Through international collaboration, researchers at KAIST have revealed that RNA editing plays a crucial role in regulating neuroinflammation, a key pathology of Parkinson's disease.
KAIST (represented by President Kwang-Hyung Lee) announced on the 27th of April that a research team led by Professor Minee L. Choi from the Department of Brain and Cognitive Sciences, in collaboration with University College London (UCL) and the Francis Crick Institute, discovered that the RNA editing enzyme ADAR1 plays an important role in controlling immune responses in astrocytes, glial cells that trigger protective reactions in the brain, and demonstrated that this mechanism is critically involved in the progression of Parkinson’s disease.
Professor Choi's research team created a co-culture model composed of astrocytes and neurons derived from stem cells originating from Parkinson's disease patients, in order to study the inflammatory responses of brain immune cells. They then treated the model with α-synuclein aggregates, which are known to cause Parkinson’s disease, and analyzed how the immune cells' inflammatory responses changed.
< Figure 1. Schematic diagram of the inflammatory RNA editing model in Parkinson's disease >
As a result, it was found that early pathological forms of α-synuclein, known as oligomers, activated the Toll-like receptor pathway, which acts as a danger sensor in astrocytes, as well as the interferon response pathway, an immune signaling network that combats viruses and pathogens. During this process, the RNA editing enzyme ADAR1 was expressed and transformed into an isoform with an altered protein structure and function.
Notably, the RNA editing activity of ADAR1, which normally functions to regulate immune responses during viral infections by converting adenosine (A) to inosine (I) through a process known as A-to-I RNA editing, was found to be abnormally focused on genes that cause inflammation rather than operating under normal conditions. This phenomenon was observed not only in the patient-derived neuron models but also in postmortem brain tissues from actual Parkinson’s disease patients.
< Figure 2. Experimental design and inflammatory response induction in astrocytes following treatment with α-synuclein oligomers (abnormally folded protein fragments) >
This directly proves that the dysregulation of RNA editing induces chronic inflammatory responses in astrocytes, ultimately leading to neuronal toxicity and pathological progression.
This study is significant in that it newly identified the regulation of RNA editing within astrocytes as a key mechanism behind neuroinflammatory responses. In particular, it suggests that ADAR1 could serve as a novel genetic target for the treatment of Parkinson’s disease.
It is also noteworthy that the study reflected actual pathological characteristics of patients by utilizing patient-specific induced pluripotent stem cell-based precision models for brain diseases.
Professor Minee L. Choi stated, “This study demonstrates that the regulator of inflammation caused by protein aggregation operates at the new layer of RNA editing, offering a completely different therapeutic strategy from existing approaches to Parkinson's disease treatment." She further emphasized, “RNA editing technology could become an important turning point in the development of therapeutics for neuroinflammation.”
< Figure 3. When treated with α-synuclein oligomers, the causative agent of Parkinson's disease, A-to-I RNA editing is induced to change genetic information by ADAR in patient-derived stem cell-differentiated glial cells, confirming that α-synuclein is likely to be associated with the progression of Parkinson's disease through RNA editing >
This study was published in Science Advances on April 11, with Professor Choi listed as a co-first author.
Paper Title: Astrocytic RNA editing regulates the host immune response to alpha-synuclein, Science Advances Vol.11, Issue 15. (DOI:10.1126/sciadv.adp8504)
Lead Authors: Karishma D’Sa (UCL, Co-First Author), Minee L. Choi (KAIST, Co-First Author), Mina Ryten (UCL, Corresponding Author), Sonia Gandhi (Francis Crick Institute, University of Cambridge, Corresponding Author)
This research was supported by the Brain Research Program and the Excellent Young Researcher Program of the National Research Foundation of Korea, as well as KAIST’s Daekyo Cognitive Enhancement Program.
2025.05.02 View 327 -
KAIST sends out Music and Bio-Signs of Professor Kwon Ji-yong, a.k.a. G-Dragon, into Space to Pulsate through Universe and Resonate among Stars
KAIST (President Kwang-Hyung Lee) announced on the 10th of April that it successfully promoted the world’s first ‘Space Sound Source Transmission Project’ based on media art at the KAIST Space Research Institute on April 9th through collaboration between Professor Jinjoon Lee of the Graduate School of Culture Technology, a world-renowned media artist, and the global K-Pop artist, G-Dragon.
This project was proposed as part of the ‘AI Entertech Research Center’ being promoted by KAIST and Galaxy Corporation. It is a project to transmit the message and sound of G-Dragon (real name, Kwon Ji-yong), a singer/song writer affiliated with Galaxy Corporation and a visiting professor in the Department of Mechanical Engineering at KAIST, to space for the first time in the world.
This is a convergence project that combines science, technology, art, and popular music, and is a new form of ‘space culture content’ experiment that connects KAIST’s cutting-edge space technology, Professor Jinjoon Lee’s media art work, and G-Dragon’s voice and sound source containing his latest digital single, "HOME SWEET HOME".
< Photo 1. Professor Jinjoon Lee's Open Your Eyes Project "Iris"'s imagery projected on the 13m space antenna at the Space Research Institute >
This collaboration was planned with the theme of ‘emotional signals that expand the inner universe of humans to the outer universe.’ The image of G-Dragon’s iris was augmented through AI as a window into soul symbolizing his uniqueness and identity, and the new song “Home Sweet Home” was combined as an audio message containing the vibration of that emotion.
This was actually transmitted into space using a next-generation small satellite developed by KAIST Space Research Institute, completing a symbolic performance in which an individual’s inner universe is transmitted to outer space.
Professor Jinjoon Lee’s cinematic media art work “Iris” was unveiled at the site. This work was screened in the world’s first projection mapping method* on KAIST Space Research Institute’s 13m space antenna. This video was created using generative artificial intelligence (AI) technology based on the image of G-Dragon's iris, and combined with sound using the data of the sounds of Emile Bell rings – the bell that holds a thousand years of history, it presented an emotional art experience that transcends time and space.
*Projection Mapping: A technology that projects light and images onto actual structures to create visual changes, and is a method of expression that artistically reinterprets space.
This work is one of the major research achievements of KAIST TX Lab and Professor Lee based on new media technology based on biometric data such as iris, heartbeat, and brain waves.
Professor Jinjoon Lee said, "The iris is a symbol that reflects inner emotions and identity, so much so that it is called the 'mirror of the soul,' and this work sought to express 'the infinite universe seen from the inside of humanity' through G-Dragon's gaze."
< Photo 2. (From left) Professor Jinjoon Lee of the Graduate School of Culture Technology and G-Dragon (Visiting Professor Kwon Ji-yong of the Department of Mechanical Engineering) >
He continued, "The universe is a realm of technology as well as a stage for imagination and emotion, and I look forward to an encounter with the unknown through a new attempt to speak of art in the language of science including AI and imagine science in the form of art." “G-Dragon’s voice and music have now begun their journey to space,” said Yong-ho Choi, Galaxy Corporation’s Chief Happiness Officer (CHO). “This project is an act of leaving music as a legacy for humanity, while also having an important meaning of attempting to communicate with space.” He added, “This is a pioneering step to introduce human culture to space, and it will remain as a monumental performance that opens a new chapter in the history of music comparable to the Beatles.”
Galaxy Corporation is leading the future entertainment technology industry through its collaboration with KAIST, and was recently selected as the only entertainment technology company in a private meeting with Microsoft CEO Nadella. In particular, it is promoting the globalization of AI entertainment technology, receiving praise as a “pioneer of imagination” for new forms of AI entertainment content, including the AI contents for the deceased.
< Photo 3. Photo of G-Dragon's Home Sweet Home being sent into the space via Professor Jinjoon Lee's Space Sound Source Transmission Project >
Through this project, KAIST Space Research Institute presented new possibilities for utilizing satellite technology, and showed a model for science to connect with society in a more popular way.
KAIST President Kwang-Hyung Lee said, “KAIST is a place that always supports new imaginations and challenges,” and added, “We will continue to strive to continue creative research that no one has ever thought of, like this project that combines science, technology, and art.”
In the meantime, Galaxy Corporation, the agency of G-Dragon’s Professor Kwon Ji-yong, is an AI entertainment company that presents a new paradigm based on IP, media, tech, and entertainment convergence technology.
2025.04.10 View 1480 -
KAIST, Galaxy Corporation Hold Signboard Ceremony for ‘AI Entertech Research Center’
KAIST (President Kwang-Hyung Lee) announced on the 9th that it will hold a signboard ceremony for the establishment of the ‘AI Entertech Research Center’ with the artificial intelligence entertech company, Galaxy Corporation (CEO Yong-ho Choi) at the main campus of KAIST.
< (Galaxy Corporation, from center to the left) CEO Yongho Choi, Director Hyunjung Kim and related persons / (KAIST, from center to the right) Professor SeungSeob Lee of the Department of Mechanical Engineering, Provost and Executive Vice President Gyun Min Lee, Dean Jung Kim of the Department of Mechanical Engineering and Professor Yong Jin Yoon of the same department >
This collaboration is a part of KAIST’s art convergence research strategy and is an extension of its efforts to lead future K-Culture through the development of creative cultural content based on science and technology. Beyond simple technological development, KAIST has been continuously implementing the convergence model of ‘Tech-Art’ that expands the horizon of the content industry through the fusion of emotional technology and cultural imagination.
Previously, KAIST established the ‘Sumi Jo Performing Arts Research Center’ in collaboration with world-renowned soprano Sumi Jo, a visiting professor, and has been leading the convergence research of art and engineering, such as AI-based interactive performance technology and immersive content. The establishment of the ‘AI Entertech Research Center’ this time is being evaluated as a new challenge for the technological expansion of the K-content industry.
In addition, the role of singer G-Dragon (real name Kwon Ji-yong), an artist affiliated with Galaxy Corporation and a visiting professor in the Department of Mechanical Engineering at KAIST, was also a major factor. Since being appointed to KAIST last year, Professor Kwon has been actively promoting the establishment of a research center and soliciting KAIST research projects through his agency to develop the ‘AI Entertech’ field, which fuses entertainment and cutting-edge technology.
< (Galaxy Corporation, from center to the left) CEO Yongho Choi, Director Hyunjung Kim and related persons / (KAIST, from center to the right) Professor SeungSeob Lee of the Department of Mechanical Engineering, Provost and Executive Vice President Gyun Min Lee, Dean Jung Kim of the Department of Mechanical Engineering and Professor Yong Jin Yoon of the same department >
The AI Entertech Research Center is scheduled to officially launch in the third quarter of this year, and this inauguration ceremony was held in line with Professor Kwon Ji-yong’s schedule to visit KAIST. Galaxy Corporation recently had a private meeting with Microsoft (MS) CEO Nadella as the only entertech company, and is actively promoting the globalization of AI entertech. In addition, since last year, it has established a cooperative relationship with KAIST and plans to actively seek the convergence of entertech and technology that transcends time and space through the establishment of a research center.
Professor Kwon Ji-yong will attend the ‘Innovate Korea 2025’ event co-hosted by KAIST, Herald Media Group, and the National Research Council of Science and Technology, held at the KAIST Lyu Keun-Chul Sports Complex in the afternoon of the same day, and will give a special talk on the topic of ‘The Future of AI Entertech.’ In addition to Professor Kwon, Professor SeungSeob Lee of the Department of Mechanical Engineering at KAIST, Professor Sang-gyun Kim of Kyunghee University, and CEO Yong-ho Choi of Galaxy Corporation will also participate in this talk show.
The two organizations signed an MOU last year to jointly research science and technology for the global spread of K-pop, and the establishment of this research center is the first tangible result of this. Once the research center is fully operational, various projects such as the development of an AI-based entertech platform and joint research on global content technology will be promoted.
< A photo of Professor Kwon Ji-yong (right) from at the talk show with KAIST President Kwang-Hyung Lee (left) from the previous year >
Yong-ho Choi, Galaxy Corporation CHO (Chief Happiness Officer), said, “This collaboration is the starting point for providing a completely new entertainment experience to fans around the world by grafting KAIST AI and cutting-edge technologies onto the fandom platform,” and added, “The convergence of AI and entertech is not just technological advancement; it is a driving force for innovation that enriches human life.”
Kwang-Hyung Lee, KAIST President, said, “I am confident that KAIST’s scientific and technological capabilities, combined with Professor Kwon Ji-yong’s global sensibility, will lead the technological evolution of K-culture,” and added, “I hope that KAIST’s spirit of challenge and research DNA will create a new wave in the entertech market.”
Meanwhile, Galaxy Corporation, the agency of Professor G-Dragon Kwon Ji-yong, is an AI entertainment technology company that presents a new paradigm based on IP, media, tech, and entertainment convergence technology. (End)
2025.04.09 View 1001 -
KAIST Identifies Master Regulator Blocking Immunotherapy, Paving the Way for a New Lung Cancer Treatment
Immune checkpoint inhibitors, a class of immunotherapies that help immune cells attack cancer more effectively, have revolutionized cancer treatment. However, fewer than 20% of patients respond to these treatments, highlighting the urgent need for new strategies tailored to both responders and non-responders.
KAIST researchers have discovered that 'DEAD-box helicases 54 (DDX54)', a type of RNA-binding protein, is the master regulator that hinders the effectiveness of immunotherapy—opening a new path for lung cancer treatment. This breakthrough technology has been transferred to faculty startup BioRevert Inc., where it is currently being developed as a companion therapeutic and is expected to enter clinical trials by 2028.
< Photo 1. (From left) Researcher Jungeun Lee, Professor Kwang-Hyun Cho and Postdoctoral Researcher Jeong-Ryeol Gong of the Department of Bio and Brain Engineering at KAIST >
KAIST (represented by President Kwang-Hyung Lee) announced on April 8 that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering had identified DDX54 as a critical factor that determines the immune evasion capacity of lung cancer cells. They demonstrated that suppressing DDX54 enhances immune cell infiltration into tumors and significantly improves the efficacy of immunotherapy.
Immunotherapy using anti-PD-1 or anti-PD-L1 antibodies is considered a powerful approach in cancer treatment. However, its low response rate limits the number of patients who actually benefit.
To identify likely responders, tumor mutational burden (TMB) has recently been approved by the FDA as a key biomarker for immunotherapy. Cancers with high mutation rates are thought to be more responsive to immune checkpoint inhibitors. However, even tumors with high TMB can display an “immune-desert” phenotype—where immune cell infiltration is severely limited—resulting in poor treatment responses.
< Figure 1. DDX54 was identified as the master regulator that induces resistance to immunotherapy by orchestrating suppression of immune cell infiltration through cancer tissues as lung cancer cells become immune-evasive >
Professor Kwang-Hyun Cho's research team compared transcriptome and genome data of lung cancer patients with immune evasion capabilities through gene regulatory network analysis (A) and discovered DDX54, a master regulator that induces resistance to immunotherapy (B-F).
This study is especially significant in that it successfully demonstrated that suppressing DDX54 in immune-desert lung tumors can overcome immunotherapy resistance and improve treatment outcomes.
The team used transcriptomic and genomic data from immune-evasive lung cancer patients and employed systems biology techniques to infer gene regulatory networks. Through this analysis, they identified DDX54 as a central regulator in the immune evasion of lung cancer cells.
In a syngeneic mouse model, the suppression of DDX54 led to significant increases in the infiltration of anti-cancer immune cells such as T cells and NK cells, and greatly improved the response to immunotherapy.
Single-cell transcriptomic and spatial transcriptomic analyses further showed that combination therapy targeting DDX54 promoted the differentiation of T cells and memory T cells that suppress tumors, while reducing the infiltration of regulatory T cells and exhausted T cells that support tumor growth.
< Figure 2. In the syngeneic mouse model made of lung cancer cells, it was confirmed that inhibiting DDX54 reversed the immune-evasion ability of cancer cells and enhanced the sensitivity to anti-PD-1 therapy >
In a syngeneic mouse model made of lung cancer cells exhibiting immunotherapy resistance, the treatment applied after DDX54 inhibition resulted in statistically significant inhibition of lung cancer growth (B-D) and a significant increase in immune cell infiltration into the tumor tissue (E, F).
The mechanism is believed to involve DDX54 suppression inactivating signaling pathways such as JAK-STAT, MYC, and NF-κB, thereby downregulating immune-evasive proteins CD38 and CD47. This also reduced the infiltration of circulating monocytes—which promote tumor development—and promoted the differentiation of M1 macrophages that play anti-tumor roles.
Professor Kwang-Hyun Cho stated, “We have, for the first time, identified a master regulatory factor that enables immune evasion in lung cancer cells. By targeting this factor, we developed a new therapeutic strategy that can induce responsiveness to immunotherapy in previously resistant cancers.”
He added, “The discovery of DDX54—hidden within the complex molecular networks of cancer cells—was made possible through the systematic integration of systems biology, combining IT and BT.”
The study, led by Professor Kwang-Hyun Cho, was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on April 2, 2025, with Jeong-Ryeol Gong being the first author, Jungeun Lee, a co-first author, and Younghyun Han, a co-author of the article.
< Figure 3. Single-cell transcriptome and spatial transcriptome analysis confirmed that knockdown of DDX54 increased immune cell infiltration into cancer tissues >
In a syngeneic mouse model made of lung cancer cells that underwent immunotherapy in combination with DDX54 inhibition, single-cell transcriptome (H-L) and spatial transcriptome (A-G) analysis of immune cells infiltrating inside cancer tissues were performed. As a result, it was confirmed that anticancer immune cells such as T cells, B cells, and NK cells actively infiltrated the core of lung cancer tissues when DDX54 inhibition and immunotherapy were concurrently administered.
(Paper title: “DDX54 downregulation enhances anti-PD1 therapy in immune-desert lung tumors with high tumor mutational burden,” DOI: https://doi.org/10.1073/pnas.2412310122)
This work was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Mid-Career Research Program and Basic Research Laboratory Program.
< Figure 4. The identified master regulator DDX54 was confirmed to induce CD38 and CD47 expression through Jak-Stat3, MYC, and NF-κB activation. >
DDX54 activates the Jak-Stat3, MYC, and NF-κB pathways in lung cancer cells to increase CD38 and CD47 expression (A-G). This creates a cancer microenvironment that contributes to cancer development (H) and ultimately induces immune anticancer treatment resistance.
< Figure 5. It was confirmed that an immune-inflamed environment can be created by combining DDX54 inhibition and immune checkpoint inhibitor (ICI) therapy. >
When DDX54 inhibition and ICI therapy are simultaneously administered, the cancer cell characteristics change, the immune evasion ability is restored, and the environment is transformed into an ‘immune-activated’ environment in which immune cells easily infiltrate cancer tissues. This strengthens the anticancer immune response, thereby increasing the sensitivity of immunotherapy even in lung cancer tissues that previously had low responsiveness to immunotherapy.
2025.04.08 View 1479 -
KAIST Accelerates Synthetic Microbe Design by Discovering Novel Enzymes Using AI
< (From left) Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering (top), Hongkeun Ji, PhD candidate of the Department of Chemical and Biomolecular Engineering (top), Ha Rim Kim, PhD candidate of the Department of Chemical and Biomolecular Engineering, and Dr. Gi Bae Kim of the BioProcess Engineering Research Center >
Enzymes are proteins that catalyze biochemical reactions within cells and play a pivotal role in metabolic processes. Accordingly, identifying the functions of novel enzymes is a critical task in the construction of microbial cell factories.
A KAIST research team has leveraged artificial intelligence (AI) to design novel enzymes that do not exist in nature, significantly accelerating microbial cell factory development and boosting the potential for next-generation biotechnological applications such as drug development and biofuel production.
KAIST (represented by President Kwang-Hyung Lee) announced on the 21st of April that Distinguished Professor Sang Yup Lee and his team from the Department of Chemical and Biomolecular Engineering have published a review titled “Enzyme Functional Classification Using Artificial Intelligence,” which outlines the advancement of AI-based enzyme function prediction technologies and analyzes how AI has contributed to the discovery and design of new enzymes.
Professor Lee’s team systematically reviewed the development of enzyme function prediction technologies utilizing machine learning and deep learning, offering a comprehensive analysis.
From sequence similarity-based prediction methods to the integration of convolutional neural networks (CNNs), recurrent neural networks (RNNs), graph neural networks (GNNs), and transformer-based large language models, the paper covers a broad range of AI applications. It analyzes how these technologies extract meaningful information from protein sequences and enhance prediction accuracy.
In particular, enzyme function prediction using deep learning goes beyond simple sequence similarity analysis. By automatically extracting structural and evolutionary features embedded in amino acid sequences, deep learning enables more precise predictions of catalytic functions.
This highlights the unique advantages of AI models compared to traditional bioinformatics approaches.
Moreover, the review suggests that the advancement of generative AI will move future research beyond predicting existing functions to generating entirely new enzymes with functions not found in nature. This shift is expected to profoundly impact the trajectory of biotechnology and synthetic biology.
< Figure 1. Extraction of enzyme characteristics and function prediction using various deep learning structures >
Ha Rim Kim, a Ph.D. candidate and co-first author from the Department of Chemical and Biomolecular Engineering, stated, “AI-based enzyme function prediction and enzyme design are highly important across various fields including metabolic engineering, synthetic biology, and healthcare.”
Distinguished Professor Sang Yup Lee added, “AI-powered enzyme function prediction shows the potential to solve diverse biological problems and will significantly contribute to accelerating research across the entire field.”
The review was published on March 28 in Trends in Biotechnology, a leading biotechnology journal issued by Cell Press.
※ Title: Enzyme Functional Classification Using Artificial Intelligence
※DOI: https://doi.org/10.1016/j.tibtech.2025.03.003
※ Author Information: Ha Rim Kim (KAIST, Co-first author), Hongkeun Ji (KAIST, Co-first author), Gi Bae Kim (KAIST, Third author), Sang Yup Lee (KAIST, Corresponding author)
This research was supported by the Ministry of Science and ICT under the project Development of Core Technologies for Advanced Synthetic Biology to Lead the Bio-Manufacturing Industry (aimed at replacing petroleum-based chemicals), and also by joint support from the Ministry of Science and ICT and the Ministry of Health and Welfare for the project Development of Novel Antibiotic Structures Using Deep Learning-Based Synthetic Biology.
2025.04.07 View 358 -
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 View 4201 -
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 View 1422 -
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 View 1233 -
KAIST Captures Hot Holes: A Breakthrough in Light-to-Electricity Energy Conversion
When light interacts with metallic nanostructures, it instantaneously generates plasmonic hot carriers, which serve as key intermediates for converting optical energy into high-value energy sources such as electricity and chemical energy. Among these, hot holes play a crucial role in enhancing photoelectrochemical reactions. However, they thermally dissipate within picoseconds (trillionths of a second), making practical applications challenging. Now, a Korean research team has successfully developed a method for sustaining hot holes longer and amplifying their flow, accelerating the commercialization of next-generation, high-efficiency, light-to-energy conversion technologies.
KAIST (represented by President Kwang Hyung Lee) announced on the 12th of March that a research team led by Distinguished Professor Jeong Young Park from the Department of Chemistry, in collaboration with Professor Moonsang Lee from the Department of Materials Science and Engineering at Inha University, has successfully amplified the flow of hot holes and mapped local current distribution in real time, thereby elucidating the mechanism of photocurrent enhancement.
The team designed a nanodiode structure by placing a metallic nanomesh on a specialized semiconductor substrate (p-type gallium nitride) to facilitate hot hole extraction at the surface. As a result, in gallium nitride substrates aligned with the hot hole extraction direction, the flow of hot holes was amplified by approximately two times compared to substrates aligned in other directions.
To fabricate the Au nanomesh, a polystyrene nano-bead monolayer assembly was first placed on a gallium nitride (p-GaN) substrate, and then the polystyrene nano-beads were etched to form a nanomesh template (Figure 1A). Then, a 20 nm thick gold nano-film was deposited, and the etched polystyrene nano-beads were removed to realize the gold nano-mesh structure on the GaN substrate (Figure 1B). The fabricated Au nanomesh exhibited strong light absorption in the visible range due to the plasmonic resonance effect (Figure 1C). >
Furthermore, using a photoconductive atomic force microscopy (pc-AFM)-based photocurrent mapping system, the researchers analyzed the flow of hot holes in real time at the nanometer scale (one hundred-thousandth the thickness of a human hair). They observed that hot hole activation was strongest at "hot spots," where light was locally concentrated on the gold nanomesh. However, by modifying the growth direction of the gallium nitride substrate, hot hole activation extended beyond the hot spots to other areas as well.
Through this research, the team discovered an efficient method for converting light into electrical and chemical energy. This breakthrough is expected to significantly advance next-generation solar cells, photocatalysts, and hydrogen production technologies.
Professor Jeong Young Park stated, "For the first time, we have successfully controlled the flow of hot holes using a nanodiode technique. This innovation holds great potential for various optoelectronic devices and photocatalytic applications. For example, it could lead to groundbreaking advancements in solar energy conversion technologies, such as solar cells and hydrogen production. Additionally, the real-time analysis technology we developed can be applied to the development of ultra-miniaturized optoelectronic devices, including optical sensors and nanoscale semiconductor components."
The study was led by Hyunhwa Lee (PhD., KAIST Department of Chemistry) and Yujin Park (Postdoc Researcher, University of Texas at Austin Department of Chemical Engineering) as co-first authors and Professors Moonsang Lee (Inha University, Department of Materials Science and Engineering) and Jeong Young Park (KAIST, Department of Chemistry) serving as corresponding authors. The research findings were published online in Science Advances on March 7.
(Paper Title: “Reconfiguring hot-hole flux via polarity modulation of p-GaN in plasmonic Schottky architectures”, DOI: https://www.science.org/doi/10.1126/sciadv.adu0086)
This research was supported by the National Research Foundation of Korea (NRF).
2025.03.17 View 1899 -
KAIST perfectly reproduces Joseon-era Irworobongdo without pigments
Typically, chemical pigments that absorb specific wavelengths of light within the visible spectrum are required to produce colors. However, KAIST researchers have successfully reproduced the Joseon-era Irworobongdo [일월오봉도] painting using ultra-precise color graphics without any chemical pigments, allowing for the permanent and eco-friendly preservation of color graphics without fading or discoloration.
< (From left) Chaerim Son, a graduate of the Department of Biochemical Engineering (lead author), Seong Kyeong Nam, a graduate of the PhD program, Jiwoo Lee, a PhD student, and Professor Shin-Hyun Kim >
KAIST (represented by President Kwang Hyung Lee) announced on the 26th of February that a research team led by Professor Shinhyun Kim from the Department of Biological and Chemical Engineering had developed a technology that enables high-resolution color graphics without using any chemical pigments by employing hemisphere-shaped microstructures.
Morpho butterflies that are brilliant blue in color or Panther chameleons that change skin color exhibit coloration without chemical pigments, as ordered nanostructures within a material reflect visible light through optical interference. Since structural colors arise from physical structures rather than chemical substances, a single material can produce a wide range of colors.
However, the artificial implementation of structural coloration is highly challenging due to the complexity of creating ordered nanostructures. Additionally, it is difficult to produce a variety of colors and to pattern them precisely into complex designs.
< Figure 1. Principle of structural color expression using micro-hemispheres (left) and method of forming micro-hemisphere patterns based on photolithography (right) >
Professor Kim’s team overcame these challenges by using smooth-surfaced hemispherical microstructures instead of ordered nanostructures, enabling the high-precision patterning of diverse structural colors.
When light enters the inverted hemispherical microstructures, the portion of light entering from the sides undergoes total internal reflection along the curved surface, creating retroreflection. When the hemisphere diameter is approximately 10 micrometers (about one-tenth the thickness of a human hair), light traveling along different reflection paths interferes within the visible spectrum, producing structural coloration.
< Figure 2. “Irworobongdo”, the Painting of the Sun, Moon, and the Five Peaks, reproduced in fingernail size without pigment using approximately 200,000 micro-hemispheres >
The structural color can be tuned by adjusting the size of the hemispheres. By arranging hemispheres of varying sizes, much like mixing paints on a palette, an infinite range of colors can be generated.
To precisely pattern microscale hemispheres of different sizes, the research team employed photolithography* using positive photoresists** commonly used in semiconductor processing. They first patterned photoresists into micropillar structures, then induced reflow*** by heating the material, forming hemispherical microstructures.
*Photolithography: A technique used in semiconductor fabrication to pattern microscale structures.
**Positive photoresist: A photosensitive polymer that dissolves more easily in a developer solution after exposure to ultraviolet light.
***Reflow: A process in which a polymer material softens and reshapes into a curved structure when heated.
This method enables the formation of hemisphere-shaped microstructures with the desired sizes and colors in a single-step fabrication process. It also allows for the reproduction of arbitrary color graphics using a single material without any pigments.
The ultra-precise color graphics created with this technique can exhibit color variations depending on the angle of incident light or the viewing perspective. The pattern appears colored from one direction while remaining transparent from the opposite side, exhibiting a Janus effect. These structural color graphics achieve resolution comparable to cutting-edge LED displays, allowing complex color images to be captured within a fingernail-sized area and projected onto large screens.
< Figure 3. “Irworobongdo” that displays different shades depending on the angle of light and viewing direction >
Professor Shinhyun Kim, who led the research, stated, “Our newly developed pigment-free color graphics technology can serve as an innovative method for artistic expression, merging art with advanced materials. Additionally, it holds broad application potential in optical devices and sensors, anti-counterfeiting materials, aesthetic photocard printing, and many other fields.”
This research, with KAIST researcher Chaerim Son as the first author, was published in the prestigious materials science journal Advanced Materials on February 5.
(Paper title: “Retroreflective Multichrome Microdome Arrays Created by Single-Step Reflow”, DOI: 10.1002/adma.202413143 )
< Figure 4. Famous paintings reproduced without pigment: “Impression, Sunrise” (left), “Girl with a Pearl Earring” (right) >
The study was supported by the National Research Foundation of Korea through the Pioneer Converging Technology R&D Program and the Mid-Career Researcher Program.
2025.02.26 View 1928 -
KAIST achieves quantum entanglement essential for quantum error correction
Quantum computing is a technology capable of solving complex problems that classical computers struggle with. To perform accurate computations, quantum computers must correct errors that arise during operations. However, generating the quantum entanglement necessary for quantum error correction has long been considered a major challenge.
< Photo 1. (From left) Students Young-Do Yoon and Chan Roh of the Master's and Doctoral Integrated Program of the Department of Physics poses with Professor Young-Sik Ra and Student Geunhee Gwak of the same program >
KAIST (represented by President Kwang Hyung Lee) announced on the 25th of February that a research team led by Professor Young-Sik Ra from the Department of Physics has successfully implemented a three-dimensional cluster quantum entangled state, a key component for quantum error correction, through experimental demonstration.
Measurement-based quantum computing is an emerging paradigm that implements quantum computations by measuring specially entangled cluster states. The core of this approach lies in the generation of these cluster quantum entangled states, with two-dimensional cluster states commonly used for universal quantum computing.
However, to advance towards fault-tolerant quantum computing, which can correct quantum errors occurring during computations, a more complex three-dimensional cluster state is required. While previous studies have reported the generation of two-dimensional cluster states, experimental implementation of the three-dimensional cluster states necessary for fault-tolerant quantum computing had remained elusive due to the extreme complexity of their entanglement structure.
< Figure 1. (a) Experimental schematic. A pulse laser with a wavelength of 800 nm is converted into a pulse laser with a wavelength of 400 nm through second harmonic generation, and this is incident on a nonlinear crystal (PPKTP) to generate multiple quantum entanglement sources. (b) Generation of a 3D cluster state through optical mode basis change >
The research team overcame this challenge by developing a technique to control femtosecond time-frequency modes, successfully generating a three-dimensional cluster quantum entangled state for the first time.
The team directed a femtosecond laser into a nonlinear crystal, simultaneously generating quantum light sources across multiple frequency modes. (A femtosecond laser is a device that emits ultrashort, high-intensity light pulses.) Using this approach, they successfully created a three-dimensional cluster quantum entangled state.
Professor Young-Sik Ra noted, “This study marks the first successful demonstration of a three-dimensional cluster quantum entangled state, which was previously difficult to achieve with existing technology. This breakthrough is expected to serve as a crucial stepping stone for future research in measurement-based and fault-tolerant quantum computing.”
< Figure 2. Results of 3D cluster state generation. (a) Nullifier measurement of the cluster state. (b) 3D cluster state reconstructed using quantum state tomography. (c) Confirmation of quantum entanglement characteristics of the 3D cluster state >
The study was published online in Nature Photonics on February 24, 2025. The first author is Chan Roh, a Ph.D. candidate in KAIST’s integrated master’s and doctoral program, with Geunhee Gwak and Youngdo Yoon contributing as co-authors. (Paper title: “Generation of Three-Dimensional Cluster Entangled State”, DOI: 10.1038/s41566-025-01631-2)
This research was supported by the National Research Foundation of Korea (Quantum Computing Technology Development Program, Mid-Career Researcher Support Program, and Quantum Simulator for Materials Innovation Program), the Institute for Information & Communications Technology Planning & Evaluation (Quantum Internet Core Technology Program, University ICT Research Center Support Program), and the U.S. Air Force Research Laboratory.
2025.02.25 View 1193 -
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 View 2387