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AI-Engineered "Nasal Spray Antiviral Platform" Developed to Block Flu and COVID-19
<(From Left) Professor Hyun Jung Chung, Professor Ho Min Kim, Professor Ji Eun Oh>
<(From Left) Dr. Seungju Yang, Dr. Jeongwon Yun, Ph.D candidate Jae Hyuk Kwon>
Respiratory viruses that have diverse strains and mutate rapidly, such as influenza and COVID-19, are difficult to block perfectly with vaccines alone. To solve this problem, KAIST's research team has successfully developed a nasal (intranasal) antiviral platform using AI technology to overcome the existing limitations of interferon-lambda treatments—namely, being "weak against heat and disappearing quickly from the nasal mucosa."
KAIST announced on December 15th that a joint research team—consisting of Professor Ho Min Ktim and Professor Hyun Jung Chung from the Department of Biological Sciences, and Professor Ji Eun Oh from the Graduate School of Medical Science and Engineering used AI to stably redesign the interferon-lambda protein and combined it with a delivery technology that ensures effective diffusion and long-term retention in the nasal mucosa, thereby implementing a universal prevention technology for various respiratory viruses.
Interferon-lambda is an innate immune protein produced by the body to block viral infections, playing a crucial role in stopping respiratory viruses like the common cold, flu, and COVID-19. However, when formulated as a treatment for nasal administration, its actual efficacy was limited by its vulnerability to heat, degrading enzymes, mucus, and ciliary motion.
The research team used AI protein design technology to precisely reinforce the structural weaknesses of interferon-lambda.
First, they significantly increased stability by changing the loose "loop" structures of the protein—which were prone to instability—into rigid "helix" structures that lock in place like a firm spring.
Additionally, to prevent "aggregation" (proteins sticking together to form lumps), they applied "surface engineering" to make the surface more water-compatible. They also introduced "glycoengineering," adding sugar chain (glycan) structures to the protein surface to make it even more robust and stable.
As a result, the newly produced interferon-lambda showed a massive improvement in stability, surviving for two weeks 50℃ and demonstrated the ability to diffuse rapidly even through thick nasal mucus.
The research team further protected the protein by encapsulating it in microscopic "nanoliposomes" and coated the surface with "low-molecular-weight chitosan." This significantly enhanced "mucoadhesion," allowing the treatment to stick to the nasal lining for an extended period.
When this delivery platform was applied to animal models infected with influenza, a powerful inhibitory effect was confirmed, with the virus level in the nasal cavity decreasing by more than 85%.
This technology is a mucosal immune platform that can block viral infections in their early stages simply by spraying it into the nose. It is expected to be a new therapeutic strategy that can respond quickly not only to seasonal flu but also to unexpected new or mutant viruses.
Professor Ho Min Kim stated, "Through AI-based protein design and mucosal delivery technology, we have simultaneously overcome the stability and retention time limitations of existing interferon-lambda treatments. This platform, which is stable at high temperatures and stays in the mucosa for a long time, is an innovative technology that can be used even in developing countries lacking strict cold-chain infrastructure. It also has great scalability for developing various treatments and vaccines." He added, "This is a meaningful achievement resulting from multidisciplinary convergence research, covering everything from AI protein design to drug delivery optimization and immune evaluation through infection models."
This research involved Dr. Jeongwon Yun from the KAIST InnoCORE (AI-Co-Research & Eudcation for innovative Drug Institute, AI-CRED Institute) Dr. Seungju Yang from the Department of Biological Sciences, and PhD student Jae Hyuk Kwon from the Graduate School of Medical Science and Engineering as co-first authors. The results were published consecutively in the renowned international journals Advanced Science (Nov 20) and Biomaterials Research (Nov 21).
Paper 1: Computational Design and Glycoengineering of Interferon-Lambda for Nasal Prophylaxis against Respiratory Viruses, Advanced Science, DOI: 10.1002/advs.202506764
Paper 2: Intranasal Nanoliposomes Delivering Interferon Lambda with Enhanced Mucosal Retention as an Antiviral, Biomaterials Research, DOI: 10.34133/bmr.0287
This research was conducted with support from the KAIST InnoCORE Program, Mid-Career Researcher Support Program and the Bio-Medical Technology Development Program through the National Research Foundation of Korea (NRF), Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the KAIST Convergence Research Institute Operation Program, and the Institute for Basic Science (IBS).
2025.12.15 View 1476 -
KAIST-UIUC researchers develop a treatment platform to disable the ‘biofilm’ shield of superbugs
< (From left) Ph.D. Candidate Joo Hun Lee (co-author), Professor Hyunjoon Kong (co-corresponding author) and Postdoctoral Researcher Yujin Ahn (co-first author) from the Department of Chemical and Biomolecular Engineering of the University of Illinois at Urbana-Champaign and Ju Yeon Chung (co-first author) from the Integrated Master's and Doctoral Program, and Professor Hyun Jung Chung (co-corresponding author) from the Department of Biological Sciences of KAIST >
A major cause of hospital-acquired infections, the super bacteria Methicillin-resistant Staphylococcus aureus (MRSA), not only exhibits strong resistance to existing antibiotics but also forms a dense biofilm that blocks the effects of external treatments. To meet this challenge, KAIST researchers, in collaboration with an international team, successfully developed a platform that utilizes microbubbles to deliver gene-targeted nanoparticles capable of break ing down the biofilms, offering an innovative solution for treating infections resistant to conventional antibiotics.
KAIST (represented by President Kwang Hyung Lee) announced on May 29 that a research team led by Professor Hyun Jung Chung from the Department of Biological Sciences, in collaboration with Professor Hyunjoon Kong's team at the University of Illinois, has developed a microbubble-based nano-gene delivery platform (BTN MB) that precisely delivers gene suppressors into bacteria to effectively remove biofilms formed by MRSA.
The research team first designed short DNA oligonucleotides that simultaneously suppress three major MRSA genes, related to—biofilm formation (icaA), cell division (ftsZ), and antibiotic resistance (mecA)—and engineered nanoparticles (BTN) to effectively deliver them into the bacteria.
< Figure 1. Effective biofilm treatment using biofilm-targeting nanoparticles controlled by microbubbler system. Schematic illustration of BTN delivery with microbubbles (MB), enabling effective permeation of ASOs targeting bacterial genes within biofilms infecting skin wounds. Gene silencing of targets involved in biofilm formation, bacterial proliferation, and antibiotic resistance leads to effective biofilm removal and antibacterial efficacy in vivo. >
In addition, microbubbles (MB) were used to increase the permeability of the microbial membrane, specifically the biofilm formed by MRSA. By combining these two technologies, the team implemented a dual-strike strategy that fundamentally blocks bacterial growth and prevents resistance acquisition.
This treatment system operates in two stages. First, the MBs induce pressure changes within the bacterial biofilm, allowing the BTNs to penetrate. Then, the BTNs slip through the gaps in the biofilm and enter the bacteria, delivering the gene suppressors precisely. This leads to gene regulation within MRSA, simultaneously blocking biofilm regeneration, cell proliferation, and antibiotic resistance expression.
In experiments conducted in a porcine skin model and a mouse wound model infected with MRSA biofilm, the BTN MB treatment group showed a significant reduction in biofilm thickness, as well as remarkable decreases in bacterial count and inflammatory responses.
< Figure 2. (a) Schematic illustration on the evaluation of treatment efficacy of BTN-MB gene therapy. (b) Reduction in MRSA biofilm mass via simultaneous inhibition of multiple genes. (c, d) Antibacterial efficacy of BTN-MB over time in a porcine skin infection biofilm model. (e) Schematic of the experimental setup to verify antibacterial efficacy in a mouse skin wound infection model. (f) Wound healing effects in mice. (g) Antibacterial effects at the wound site. (h) Histological analysis results. >
These results are difficult to achieve with conventional antibiotic monotherapy and demonstrate the potential for treating a wide range of resistant bacterial infections.
Professor Hyun Jung Chung of KAIST, who led the research, stated, “This study presents a new therapeutic solution that combines nanotechnology, gene suppression, and physical delivery strategies to address superbug infections that existing antibiotics cannot resolve. We will continue our research with the aim of expanding its application to systemic infections and various other infectious diseases.”
< (From left) Ju Yeon Chung from the Integrated Master's and Doctoral Program, and Professor Hyun Jung Chung from the Department of Biological Sciences >
The study was co-first authored by Ju Yeon Chung, a graduate student in the Department of Biological Sciences at KAIST, and Dr. Yujin Ahn from the University of Illinois. The study was published online on May 19 in the journal, Advanced Functional Materials.
※ Paper Title: Microbubble-Controlled Delivery of Biofilm-Targeting Nanoparticles to Treat MRSA Infection ※ DOI: https://doi.org/10.1002/adfm.202508291
This study was supported by the National Research Foundation and the Ministry of Health and Welfare, Republic of Korea; and the National Science Foundation and National Institutes of Health, USA.
2025.05.29 View 8062