Biomolecules & Therapeutics最新文献

{"title":"Exploring the Regenerative Role of Exosomes as a Potential Therapy for Peripheral Nerve Injury: A Systematic Review.","authors":"Anita Soraya Soetoko, Dwi Cahyani Ratna Sari, Arta Farmawati, Nur Arfian, Dhite Bayu Nugroho","doi":"10.4062/biomolther.2026.218","DOIUrl":"10.4062/biomolther.2026.218","url":null,"abstract":"<p><p>Exosomes are nano-sized extracellular vesicles loaded with bioactive cargo that mediate intercellular communication. Their emerging role in tissue regeneration has garnered increasing attention, especially in the context of peripheral nerve injury (PNI), which poses a significant therapeutic challenge. Although many studies have explored exosome-based therapies for PNI, the findings are often fragmented and lack a comprehensive synthesis. This systematic review aims to synthesize the current evidence and elucidate the molecular mechanisms through which exosomes contribute to neural regeneration. This systematic review, conducted in accordance with PRISMA 2020 guidelines, included 33 eligible studies identified through Scopus, ScienceDirect, PubMed, and Google Scholar. Exosomes derived from diverse cellular sources were assessed for their capacity to enhance repair outcomes. Reported cargo, including miRNAs and neurotrophic factors, has been shown to activate key signaling pathways that promote neurite outgrowth, modulate Schwann cell and immune responses, stimulate angiogenesis, and activate perineurial cells. By orchestrating these processes, exosomes emerge as a promising therapeutic strategy to enhance nerve regeneration and functional recovery.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 5","pages":"1103-1118"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of ATOH8 in Mitigating Cardiac Fibrosis in Heart Failure via Inhibition of the Transcriptional Repression of Smad7 by RUNX2.","authors":"Chong Chen, Yapan Yang, Chengyingjie Yang, Chuanyu Gao, Yuhao Liu, Honghui Yang, Xiaohu Wang, Yachen Zhang, Zhuowang Ge","doi":"10.4062/biomolther.2026.044","DOIUrl":"10.4062/biomolther.2026.044","url":null,"abstract":"<p><p>Cardiac fibrosis is a major driver of heart failure and a key therapeutic target. Here, we demonstrated the role of atonal homologue 8 (ATOH8) in the modulation of cardiac fibrosis in heart failure. The expression of ATOH8 was significantly reduced in patients with heart failure and in the left ventricular tissues of model mice. ATOH8 silencing resulted in the worsening of fibrosis, and adenovirus- induced overexpression of ATOH8 attenuated the progression of cardiac fibrosis under <i>in vitro</i> conditions. RNA sequencing analysis demonstrated that ATOH8 potentially influences cardiac fibrosis by modulating the TGF-/Smad signaling pathway. This was verified through ATOH8 silencing experiments, which showed a marked reduction in the expression of Smad7-a known inhibitor of fibrosis. Further investigation into the molecular mechanisms via immunoprecipitation mass spectrometry indicated that ATOH8 can directly bind to the transcription factor RUNX2, which was found to directly interact with the promoter region of Smad7 to suppress its expression. Accordingly, ATOH8 silencing was found to enhance RUNX2-mediated transcriptional repression of Smad7. The findings collectively imply that ATOH8 attenuates cardiac fibrosis through the RUNX2/Smad7 axis, although interactions with other fibrotic proteins need to be explored further. Through <i>in vivo</i> experiments in model mice of heart failure, we were able to demonstrate that the targeted overexpression of ATOH8 in fibroblasts via adeno-associated virus-9 carrying periostin significantly alleviated cardiac fibrosis and dysfunction induced by transverse aortic constriction surgery. Thus, the findings presented here indicate that ATOH8 potentially represents a novel biomarker and therapeutic target for the attenuation of cardiac fibrosis.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 5","pages":"1148-1162"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT6 Mediates Sterol-Dependent Feedback Regulation of Cholesterol Biosynthetic Genes in Hepatocytes.","authors":"Yeonsoo Kim, Ye Eun Cho, Hyeokjin Lim, Yunseo Park, Seonghwan Hwang","doi":"10.4062/biomolther.2026.046","DOIUrl":"10.4062/biomolther.2026.046","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by lipotoxic hepatocellular injury, inflammation, and fibrosis, with excess hepatic cholesterol contributing to disease pathogenesis. While the SCAP-INSIG-SREBP2 pathway classically regulates cholesterol biosynthetic gene expression via sterol sensing at the endoplasmic reticulum, the epigenetic mechanisms coupling cellular sterol status to gene expression remain unclear. Here, we investigated the role of sirtuin 6 (SIRT6), a nuclear histone deacetylase, in sterol-induced feedback regulation of cholesterol biosynthetic genes in hepatocytes. In HepG2 and AML12 cells, 25-hydroxycholesterol (25-HC) reduced the expression of SREBP2 and downstream cholesterol biosynthetic genes, including HMGCR and HMGCS1. This repression was associated with SIRT6 activation, as evidenced by reduced acetylation of histone H3 lysine 9 and lysine 56. Pharmacological SIRT6 inhibition reversed the repression of cholesterol biosynthetic genes, whereas SIRT6 activators phenocopied the inhibitory effects of 25-HC on the SREBP2 pathway. Conversely, sterol depletion via lovastatin inhibited SIRT6 activity, leading to the compensatory upregulation of cholesterol biosynthetic genes. Notably, SIRT6 overexpression or pharmacological activation reversed lovastatin-induced upregulation of SREBP2 and its target genes. These findings establish SIRT6 as a sterol-responsive nuclear regulator that converts intracellular cholesterol status into epigenetic repression of the cholesterol biosynthetic program. This SIRT6-dependent pathway complements endoplasmic reticulum-based sterol sensing and provides a mechanistic insight into hepatic cholesterol dysregulation in MASH.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 5","pages":"1136-1147"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Nerve Injury and Denervation-Induced Sarcopenia with a Focus on Pharmacological Dual-Target Strategies.","authors":"Chawon Yun, Jun Hong Won, So Young Lee, Tae Hwan Kim, Ga Hee Kim, Jung Il Lee","doi":"10.4062/biomolther.2026.047","DOIUrl":"10.4062/biomolther.2026.047","url":null,"abstract":"<p><p>Peripheral nerve injury (PNI) causes rapid disruption of neuromuscular connectivity, leading to sarcopenia characterized by muscle wasting, mitochondrial dysfunction, and metabolic imbalance. Although calcium dysregulation and aberrant AMPK/mTOR signaling are known contributors, the molecular cascade linking nerve injury to muscle degeneration remains incompletely understood. This review explores pharmacological and molecular strategies to restore neuromuscular integrity after PNI. We focus on agents such as 4-aminopyridine (4-AP), a potassium channel blocker that enhances nerve conduction, and clemastine, an antihistamine that promotes Schwann cell-mediated remyelination. These compounds represent a potential dual approach to accelerating nerve repair while maintaining muscle viability. We also explore muscle-centered molecular strategies, focusing on pathways such as Forkhead box protein O (FOXO), Glycogen synthase kinase 3 beta (GSK-3β), signal transducer and activator of transcription 3 (STAT3), and TGF-β/Smad, which govern the balance between protein synthesis and degradation. Of note, most current studies suggest that phytochemicals derived from marine sources, including seaweed, may attenuate denervation-induced catabolism by modulating FOXO signaling and suppressing E3 ubiquitin ligase activity. Additionally, we highlight the critical crosstalk between motor neurons and skeletal muscle, mediated by neurotrophic factors such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and Neurotrophin-3 (NT-3), which support both neuromuscular junction stability and axonal regrowth. By integrating insights from nerve biology and muscle physiology, this review outlines a therapeutic framework that targets both nerve regeneration and muscle preservation, an approach that effectively addresses nerve injury-induced sarcopenia effectively.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 5","pages":"1087-1102"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emodin Induces AIF-Associated Apoptosis and Suppresses Wnt/β-Catenin Signaling in Colorectal Cancer Stem-Like Cells.","authors":"Mahdieh Ahmadi, Hong Lae Kim, Hye Jin Jung","doi":"10.4062/biomolther.2026.015","DOIUrl":"10.4062/biomolther.2026.015","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a major cause of cancer-related mortality due to therapeutic resistance. Because colorectal cancer stem-like cells (CRCSCs) play a central role in tumor initiation and progression, therapeutic strategies addressing CSC-enriched populations are urgently needed. In this study, we investigated the anticancer effects of emodin, a natural anthraquinone, in CSC-enriched tumorsphere models. Emodin significantly suppressed the viability and self-renewal capacity of HCT116- and SW480-derived CSCs. It induced G0/G1 cell cycle arrest and markedly downregulated stemness-associated markers (CD44, CD133, ALDH1A1, SOX2, NANOG, and OCT4). Importantly, emodin-induced cell death was characterized by mitochondrial dysfunction, increased mitochondrial reactive oxygen species, loss of membrane potential, and nuclear translocation of apoptosis-inducing factor (AIF). This cytotoxicity was not rescued by the pan-caspase inhibitor Z-VAD-FMK, confirming caspase-independent apoptosis. Furthermore, network pharmacology and experimental validation identified GSK3β as a key target. Emodin reduced Wnt/β-catenin signaling by decreasing β-catenin stabilization and nuclear accumulation. Crucially, a rescue experiment utilizing LiCl confirmed that emodin's suppressive effects are mechanistically dependent on the GSK3β/Wnt/β-catenin axis. Collectively, emodin suppresses CRCSC characteristics <i>in vitro</i> by downregulating Wnt/β-catenin signaling and inducing AIF-associated caspase-independent apoptosis, highlighting its therapeutic potential against CRC.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 5","pages":"1192-1206"},"PeriodicalIF":4.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Senescence: Emerging Therapeutic Target for Idiopathic Pulmonary Fibrosis Pathogenic Mechanisms and Therapeutic Strategies.","authors":"Nattha Suwanprakorn, Youngrok Choi, Yeong Seok Choi, Hye Jin Yoo, Su-Geun Yang","doi":"10.4062/biomolther.2026.004","DOIUrl":"10.4062/biomolther.2026.004","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis is a progressive and fatal lung disease characterized by irreversible tissue scarring, structural distortion, and declining respiratory function. Although currently approved antifibrotic therapies can slow disease progression, they do not stop or reverse fibrosis, highlighting the need to better understand upstream disease mechanisms. Increasing evidence identifies cellular senescence as a central biological process linking aging, epithelial cell vulnerability, mitochondrial dysfunction, and abnormal tissue repair in pulmonary fibrosis. Senescent epithelial and mesenchymal cells remain metabolically active and release a broad array of secreted factors that promote fibroblast activation, persistence of contractile cells, and excessive matrix deposition. Recent advances using single-cell and three-dimensional culture approaches further reveal the accumulation of transitional epithelial cell states that fail to complete normal differentiation and instead perpetuate fibrotic remodeling. These findings suggest that senescence represents not merely a consequence of tissue injury, but a self-sustaining driver of disease progression. This review integrates current mechanistic insights into how cellular senescence coordinates epithelial injury, immune dysregulation, and biomechanical feedback to drive lung fibrosis. We also discuss emerging therapeutic strategies that target senescent cells or their downstream signaling pathways, highlighting their potential to complement existing antifibrotic treatments and enable more effective disease modification.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"800-817"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Inflammation and Cancer Therapy: Molecular Mechanisms and Clinical Advances in Resolution Pharmacology.","authors":"Boram Kim, Minh Tuan Nguyen, Yongook Lee, Mi Kyung Park, Chang Hoon Lee","doi":"10.4062/biomolther.2026.018","DOIUrl":"10.4062/biomolther.2026.018","url":null,"abstract":"<p><p>Chronic inflammation is a pivotal pathophysiological process driving carcinogenesis, tumor progression, metastasis, and therapeutic resistance. While the termination of inflammation was historically viewed as a passive dissipation event, recent research has established it as an active biochemical program governed by Specialized Pro-resolving Mediators (SPMs). Based on cutting-edge research from 2022 to 2025 and clinical data, this review provides an in-depth analysis of the failure of lipid class switching, receptor signal transduction networks, the role of resolution-phase macrophages (M-res), and the Sulciner Effect. Furthermore, it highlights Resolution Pharmacology as the emerging fourth pillar of cancer therapy, particularly through nanomedicine and synergistic strategies with immune checkpoint inhibitors.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"755-763"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into Nrf2 Activation and Oxidative Stress Responses of Per- and Polyfluoroalkyl Substances (PFAS) in Human Keratinocytes.","authors":"Samantha Serafin Sevilleno, Hye Jin Park, Min Sik Choi","doi":"10.4062/biomolther.2026.009","DOIUrl":"10.4062/biomolther.2026.009","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are widely used in consumer products for their hydrophobic and chemical stability, yet their dermatotoxicological effects remain underexplored. This study investigated the ability of representative PFAS (PFBS, PFBA, PFHpA, PFOA, PFNA, PFDA, 4:2 FTOH, and 6:2 FTOH) to activate the Nrf2-Keap1-ARE signaling pathway and induce oxidative stress in human keratinocytes. Results revealed that PFOA and PFHpA tested positive for the KeratinoSens™ assay, while PFNA showed borderline activity. PFNA and 6:2 FTOH produced the highest ROS increases at sub-cytotoxic levels, decreasing at higher doses, suggesting cytotoxic stress. PFHpA, PFOA, PFBS, PFBA, 4:2 FTOH and PFDA induced relatively minor fluctuations in ROS across all concentrations. Although previously reported as negative in the murine Local Lymph Node Assay (LLNA), PFOA tested positive in both KeratinoSens™ and ROS assays, indicating activation of oxidative stress-driven cellular pathways distinct from classical immune sensitization mechanisms. <i>In silico</i> prediction failed to capture these effects, underscoring current limitations of computational toxicology for PFAS. These findings suggest that PFAS-induced oxidative stress may compromise skin barrier function and inflammatory signaling, with implications for dermatological disorders and consumer safety. These results highlight Nrf2-mediated redox signaling as a mechanistically relevant target for evaluating PFAS-induced dermatotoxicity and support the integration of pathway-based <i>in vitro</i> assays into PFAS risk assessment.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"953-961"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral and Biochemical Evaluation of a Curcumin-Loaded Nano-Liposomal Formulation in a Scopolamine-Induced Mouse Model of Cognitive Impairment.","authors":"Hwa-Young Lee, Muhammad Kamal Hossain, Gi-Hyun Jang, Hyewon Lee, Yu-Mi Kim, Han-Jung Chae","doi":"10.4062/biomolther.2026.062","DOIUrl":"10.4062/biomolther.2026.062","url":null,"abstract":"<p><p>Scopolamine-induced cognitive impairment in mice models acute cholinergic dysfunction associated with early functional features of Alzheimer's disease (AD). This study evaluated the neuroprotective potential of curcumin-loaded nanoliposomes (Cur-NL), a bioavailable curcumin formulation, using behavioral, molecular, and biochemical approaches. Male mice received oral Cur-NL (250, 500, or 1000 mg/kg) for 30 days, followed by a single intraperitoneal injection of scopolamine (2 mg/kg). Cognitive performance was assessed by the open field test and Barnes maze. Acetylcholinesterase (AChE) activity, acetylcholine (ACh) levels, hippocampal gene expression, and reactive oxygen species (ROS) accumulation were analyzed to investigate underlying mechanisms. Cur-NL significantly improved spatial learning and memory and restored cholinergic balance by normalizing AChE activity and ACh levels. Treatment also attenuated hippocampal neuroinflammation, oxidative stress, and ROS accumulation. Cur-NL modulated genes related to amyloid processing and synaptic plasticity, suppressing App and Bace1 and upregulating Adam10 and Bdnf. Network analyses supported the involvement of cholinergic, inflammatory, and synaptic signaling pathways. These findings indicate that Cur-NL confers multitarget neuroprotection in a scopolamine-induced model and may serve as a candidate for managing early cholinergic-related cognitive decline. Important limitations should be acknowledged: curcumin concentrations in plasma and brain were not quantified, and a free-curcumin comparator was not included. The findings should therefore be interpreted as evidence of efficacy of the tested Cur-NL preparation, not as a comparative demonstration of nano-liposomal superiority over free curcumin. Direct pharmacokinetic and head-to-head comparative studies are required to establish the formulation-specific contribution of nano-liposomal delivery.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"866-881"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioprocess Development of a Human Monoclonal Antibody against MERS-CoV: Analytical and Preclinical Studies.","authors":"Jongsun Lim, Hansaem Lee, Joo-Yeon Lee, Dong-Gyu Jo, Sangwon Hong, So-Young Lee, Byoung Kwon Park, Yungjun Jeong, Jimin Seo, Soya Park, Hwanui Jung, Chan Ki Park, Kyung-Chang Kim, Ickhyun Cho","doi":"10.4062/biomolther.2026.001","DOIUrl":"10.4062/biomolther.2026.001","url":null,"abstract":"<p><p>Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a zoonotic virus first identified in 2012, responsible for severe respiratory illness and a high case fatality rate of approximately 35%. MERS-CoV is primarily transmitted from dromedary camels to humans, but human-to-human transmission, particularly in healthcare settings, has led to outbreaks beyond the Middle East, including a major epidemic in South Korea in 2015. Despite its significant public health threat and potential for future outbreaks, no approved vaccines or therapeutic agents are available for MERS-CoV. To address this urgent need, the Korea National Institute of Health (KNIH) developed therapeutic monoclonal antibodies derived from B cells of convalescent MERS patients. Among these, KNIH-88, a non-receptor-binding domain (non-RBD) S1-specific antibody, was selected for preclinical development. In this study, KNIH-88 was produced with high purity under controlled manufacturing conditions and extensively characterized for structural and physicochemical properties, including molecular weight, charge, hydrophobicity, and high molecular weight (HMW) profile. KNIH-88 demonstrated strong binding affinity to MERS-CoV Spike protein and potent neutralizing activity <i>in vitro</i>. To ensure stability and facilitate rapid deployment in outbreak scenarios, a lyophilized formulation of KNIH-88 was developed, maintaining structural integrity and biological activity under long-term storage. Collectively, these findings support KNIH-88 as a promising therapeutic antibody for MERS-CoV, combining potent antiviral efficacy, structural stability, and a formulation suitable for stockpiling and emergency use in endemic regions.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"882-890"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}