Gachon University

2023 年 8 月 10 号，据 Bussiness Korea 报道，EYEGENE 公司正在计划一旦 EG-COVID-001—韩国首款新冠 mRNA 疫苗下个月在澳大利亚完成临床 2a 期试验就立即寻求外部投资进行联合开发或者技术转让。目前，EYEGENE 公司研发资金匮乏，仅澳大利亚进行的 2a 期试验就投入了 200 亿韩元的自有资金，三期临床还需要超过 1000 亿韩元的大窟窿填补，雪上加霜的是，韩国政府对 mRNA 疫苗的政策资金支持也已停止。随着新冠 mRNA 疫苗风口的过去，众多从事新冠 mRNA 疫苗研发的公司资金短缺，尤其是先前已进入临床试验的公司，更是面临进退维谷的窘境。遥想当初，韩国业内锣鼓喧天，人人撸起袖子准备大干一场。2021 年 9 月，Hanmi Pharmaceutical、GC Pharma 和 ST Pharm 三家韩国制药巨头成立 K-mRNA 联盟，其中 Hanmi 负责原料生产，GC 负责罐装，ST 负责 CDMO，旨在推进新冠 mRNA 疫苗的开发和大规模生产。同时，还有 3 家冉冉升起的 mRNA 疫苗研发初创企业也仅跟着成立 mRNA Bio 初创联盟，分别是 EYEGENE，GeneOne Life Science，Quratis。如今，聚义竖起的大旗已倒下，联盟里的成员只能各回各家，各找各妈。当初谁也不会想到，新冠 mRNA 疫苗的一片蓝海还就只容得下最早吃螃蟹的两家，对于后来者，你追的越紧，打水漂的银子越多。我们曾经介绍过 mRNA 疫苗在澳大利亚本土化的过程，本期内容主要回顾一下，从一片火热到遭遇冰点，两年多以来，mRNA 技术在韩国这片制造业发达的土地上经历了怎样的进程。2021 年 5 月 22 号，三星生物制品公司与 Moderna 公司达成协议，为其新冠 mRNA 疫苗提供大规模、商业化的灌装生产，但是，并不涉及 mRNA 疫苗本身的生产。同年 10 月，韩国卫生部批准三星生物制品公司生产的 Moderna 新冠 mRNA 疫苗用于国内紧急使用。韩国当然不会满足仅仅作为 Moderna 的初级代工，在政府资金的大力支持下，谋求短期内快速实现国产新冠 mRNA 疫苗的突破。2022 年 6 月 23 号，嘉泉大学主办并且发起新变种传染病 mRNA 疫苗项目（KmVAC），由医学院洪基钟教授任主任。该项目计划到 2025 年投资总计 900 亿韩元的研究资金，其中包括 688 亿韩元的政府捐款，宗旨是扶持韩国国内 mRNA 疫苗研发企业，完成国产 mRNA 疫苗平台的快速搭建，两年内产生进入临床试验的 mRNA 疫苗。在启动会上，多家韩国疫苗公司和研究机构对于未来 mRNA 疫苗的研究计划作了详细阐述。通过这些报告，我们能够对韩国 mRNA 疫苗行业的发展情况有一个大致的了解。👀   QuratisQuratis 成立于 2016 年，是韩国一家专门从事免疫相关疫苗开发的公司。目前，主要开发项目为适用于成人和青少年的结核病疫苗 QTP101 和自复制新冠 mRNA 疫苗 QTP104，公司正在全力加速这两款疫苗的商业化上市。QTP101 是一款针对成人和青少年的结核菌蛋白亚单位疫苗，由 ID93 和 GLA-SA 佐剂组成。ID93 是一种融合蛋白，由强毒抗原（Rv2608、Rv3619、Rv3620）和潜伏抗原（Rv1813）组成。GLA 是单磷酰脂质 A 的衍生物，是脂多糖 (LPS) 的解毒形式。它作为TLR4激动剂发挥作用，有效诱导 Th1 介导的免疫反应。QTP101 能增强人体由卡介苗形成的免疫反应，只需三剂即可预防结核病，显示出更高的安全性。QTP101 于 2021 年在韩国完成成人和青少年的 I 期临床试验，并于去年获准开展 2b/3 期临床试验。QTP104 目前正在韩国完成一期临床试验，是韩国开发的首个自复制 mRNA 疫苗。此外，Quratis 还在计划开发基于自复制 RNA 技术的下一代结核菌疫苗 QTP102。👀   国际疫苗研究所与 SK Bioscience国际疫苗研究所（Internation Vaccine Institute,IVI）是一个独立的非营利性国际组织，由联合国开发计划署 (UNDP) 倡议于 1997 年成立，其宗旨是为全球公共卫生发现、开发和提供安全、有效且负担得起的疫苗。IVI 总部位于首尔，由韩国及 39 个成员国和世界卫生组织共同主办。IVI 希望与嘉泉大学、SK Bioscience 共同来开发拉沙热 mRNA 疫苗项目。SK Bioscience 是韩国一家大型疫苗研发生产公司，于 2018 年从 SK 化学拆分出来。多年来，SK Bioscience 在疫苗领域取得众多成就，例如，于 2015 年推出韩国首个基于细胞培养的三价流感疫苗，世界上第一个基于细胞培养的四价流感疫苗，世界上第二个带状疱疹病毒疫苗和韩国第二个水痘疫苗。👀   Quad MedicineQuad Medicine 是一家拥有医疗微针平台技术的公司，该技术可用于多种用途，包括可透皮给药的疫苗、合成药物和诊断医疗设备。微针（MAP）免疫是一种通过皮肤传递抗原的方法，同时产生全身和局部免疫。Quad Medicine 希望与嘉泉大学、ST PHARM 共同协作来生产基于微针技术的新冠 mRNA 疫苗。👀   RNAGENERNAGENE 成立于 2018 年，是韩国首家从事 mRNA 疫苗/药物研发的生物公司，主要开发基于 mRNA 技术的预防性疫苗、癌症免疫疗法及蛋白替代疗法。在 2022 年，RNAGENE 与韩国国立卫生研究院签订 2 项服务合同，一个是生产编码结核分枝杆菌抗原的 mRNA，一个是开发增强适应性免疫，提升免疫持续时间的 RNA 疫苗技术。遗憾的是，迄今为止，这家公司在新冠 mRNA 疫苗研发方面并未取得任何值得引入注意的成绩，在其他管线也没有进入临床试验阶段的项目。👀   西江大学与 PhytoMabSeong-Ryong Kim (金成龍)教授是韩国首尔西江大学生命科学系植物分子生物实验室的领导者，研究方向主要集中在利用光合生物合成蛋白质，例如，利用植物表达系统生产日本脑炎病毒疫苗或者抗体药物等。2022 年，他开始主持研发寨卡病毒 mRNA 疫苗研发项目。比较特别的是，他意图将 RNA 聚合酶与加帽酶融合在一起，形成 ctDdRp，同时实现转录和加帽反应。PhytoMab 是韩国一家合成生物学公司，利用 Crispr/Cas9 技术开发了首个生产人源化生物制品的植物干细胞系。金成龍教授希望与 PhytoMab 展开合作，利用其无细胞表达体系来生产体外转录翻译所需的酶。👀   ST PHARMST PHARM 是一家成立于 1983 年的老牌韩国 CDMO 公司，为许多大型制药公司和生物公司提供 GMP 级别的活性药物成分、中间体的顶级定制化服务，拥有非常可靠的工艺开发及放大优化方面的经验。从 2020 年开始，随着新冠 mRNA 疫苗的崛起，ST PHARM 开始重点布局 mRNA 方向， 主要包括 3 个方面：mRNA 疫苗的生产制造，帽类似物生产，LNP 脂质体成分生产。👀   逆水行舟尽管今年以来韩国 mRNA 行业逐渐进入冷静期，但是，依然有人逆水行舟，持续推进。新变种染病 mRNA 疫苗项目组（KmVAC）与韩国资深 CDMO 公司 BMI Korea 签订协议，双方计划共同推进 mRNA 疫苗相关的研究和基础设施建设，该公司在 2022 年建设了年产能超过 5000 万剂的新冠 mRNA 疫苗生产线。此外，今年 3 月份，KmVAC 还与 Moderna 建立合作伙伴关系，以便更加有效地开发新发传染病 mRNA 疫苗的研发。三养生物制药公司 (Samyang Biopharmaceuticals Corporation) 成立于 1995 年，前身是三养社的制药业务。今年 4 月份，三养生物制药公司将 NanoReady 药物递送技术授权给 LG 化学，负责向其提供关键原料，双方共同开发基于 mRNA 技术的癌症疗法。👀   结论新冠 mRNA 疫苗的成功使得韩国政府、制药巨头以及初创新秀意识到 mRNA 技术即将掀起的医药革新浪潮，因此，政府牵头成立专门的项目组，给予高校和企业资金政策支持，寄希望于搭建完全国产化的 mRNA 疫苗生产线，以应对将来可能出现的新变种传染病。早期，人们普遍觉得 mRNA 疫苗研发周期短，生产简单快速，所以全部扎进国产新冠 RNA 疫苗的研发赛道，野蛮扩张产能，自信短期内便能取得突破进行商业化生产。潮水褪去，韩国首个新冠 mRNA 疫苗的临床试验面临资金不足，难以维系的困境，那些扩张的生产线也是空等一场。很多时候人们充满激情的时候，经验是远远不足的，但是，至少这种蛮干开启了韩国 mRNA 技术国产化之路。相比澳大利亚来说，韩国自身拥有非常深厚的制造业基础，因此，整个 mRNA 技术产业化要走得更加成熟。比较遗憾的是，除了新冠 mRNA 疫苗，韩国企业并未在其他方向取得任何突破性的进展。对于 mRNA 技术来说，未来两三年如果不能有其他方向的产品上市，依然只有一朵新冠 mRNA 疫苗的过气红花，那么，不仅是韩国，其他各国的 mRNA 研发/生产企业都可能会面临更加严酷的寒冬。由生物制品圈&抗体圈主办的“2023生物制品工艺发展大会”将于9月22-23日在上海举办，本次大会将主要聚焦生物制品前沿技术、CMC、生产、工艺等热点话题进行探讨交流，涉及人用疫苗、兽用疫苗、抗体药、细胞治疗、基因治疗等生物制品领域。届时将邀请生物制品领域经验权威的专家进行报告，欢迎各界同仁参会学习交流。1.会议名称：2023生物制品工艺发展大会2.会议时间：2023年9月22-23日（周五、周六）3.会议地点：上海（酒店定向通知）4.主办单位：生物制品圈、抗体圈5.媒体支持：药时空、药创客、细胞基因研究圈6.报名方式及费用：扫描识别下方二维码进行报名登记。转发分享福利：生物医药研发企业、科研院校和监管机构人员，前100位报名人员转发分享本通知至朋友圈可免费参会（不含餐饮）报名后，加微信13585867695发截图给工作人员即可。组委会获得报名信息后，根据报名信息进行初筛，并进一步与报名者沟通确认，实现精准邀请，最终有机会进入大会微信群（严格审核通过）。各类商务合作咨询：13585867695（同微信）大会日程识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

GENOA, Italy, Nov. 17, 2022 /PRNewswire/ -- The world's first simultaneous multi-channel/multi-nuclear 11.74T MRI system is currently under development at Gachon University Gil Medical Center (GUGMC). Continue Reading In operation the most innovative 11.74T MRI Core Magnet to be used on humans The world’s first simultaneous multi-channel/multi-nuclear 11.74T MRI system is currently under development at Gachon University Gil Medical Center with ASG Superconductors The world’s first simultaneous multi-channel/multi-nuclear 11.74T MRI system is currently under development at Gachon University Gil Medical Center with ASG Superconductors In the first Half of 2022 GUGMC successfully completed the Site Acceptance Test of the Magnet, which is a core part of the brain-specific ultra-precision 11.74T MRI that is being jointly developed with ASG Superconductors (ASG) in Italy. GUGMC invited technical managers of ASG and experts from Korea for performance evaluation of the 11.74T MRI Magnet. Now one of the most sophisticated magnets in the world is "in operation" and fully serviced by ASG technicians onsite. At the same time the evaluation committee confirmed that the magnetic field reached the target field density while maintaining stability and uniformity. The Site Acceptance Test evaluated three main criteria: 1) the internal temperature of the 11.74T MRI magnet (< 2.2K (Kelvin)), 2) the intensity of the magnetic field (11.74T at 2.2K) 3) the uniformity of the magnetic field. The test satisfied these three criteria allowing the project to proceed to the next step. The researchers at GUGMC are aiming to operate the world's first simultaneous multi-channel/multi-nuclear 11.74T MRI system before the end of this year combining the 11.74T magnet with gradient magnetic coils, RF coil s , electronic equipment, power supplies, etc. Brain images acquired with the 11.74T MRI are expected to be almost 10 times more detailed than those obtained from a standard 1.5T MRI, providing researchers with ultra-high-resolution images of the brain structures for the early diagnosis and treatment of neuro-degenerative brain diseases such as Parkinson's disease, Alzheimer's disease and stroke, etc. Professor Woo-Kyung KIM, President of Gachon University Gil Medical Center (President of the Neuroscience Research Institute) said, "The ultra-high resolution brain images obtained from the 11.74T MRI system are expected to provide significant clues for the early diagnosis and treatment of neuro-degenerative brain diseases such as Parkinson's disease, Alzheimer's and stroke, etc. This 11.74T project (Principal Investigator: Prof. Jun-Young CHUNG) is supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry for Health and Welfare, Korea." Stefano Pittaluga Sales Manager UHF and MRI of ASG Superconductors said, "This is another important milestone for our superconducting technology track record in a very challenging and exclusive sector like Ultra High Field MRI magnets development. Furthermore, we're very proud to collaborate with such a prestigious institute as GUGMC and we're confident that in the coming years relevant improvements in healthcare will be achieved thanks to this very sophisticated MRI technology system magnet based on our cutting edge 11.74T magnet and GUGMC's scientific work" Video - Photo - Photo - Logo - SOURCE ASG Superconductors

From immunity to metabolism to mental health, it seems like the gut microbiome has been linked to every aspect of human health and disease. But with hundreds of bacterial species populating our gastrointestinal tract, it's a daunting task to pinpoint which molecules made by which bacteria affect which biological processes -- and how they do so. From immunity to metabolism to mental health, it seems like the gut microbiome has been linked to every aspect of human health and disease. But with hundreds of bacterial species populating our gastrointestinal tract, it's a daunting task to pinpoint which molecules made by which bacteria affect which biological processes -- and how they do so. "Microbiome studies need to move from making associations to determining function and causation," said Ramnik Xavier, the Kurt J. Isselbacher Professor of Medicine in the Field of Gastroenterology at Harvard Medical School and Massachusetts General Hospital, a core institute member at the Broad Institute of MIT and Harvard, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT. Such knowledge is essential for learning how to manipulate gut bacteria to treat or prevent illness. A team led by researchers at HMS and the Broad has just accomplished the rare feat of connecting those dots for one important gut bacterium. "The real significance of this work was connecting a bacterium, the molecule it makes, the pathway it operates through, and the biological outcome," said Jon Clardy, the Hsien Wu and Daisy Yen Wu Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS and co-senior author of the study with Xavier. "That's very rare." Clardy, Xavier, and colleagues focused on Akkermansia muciniphila, a species that accounts for an impressive 3 percent of the gut microbiome. It gets its name from the intestinal mucus it breaks down. Study after study had suggested that A. muciniphila plays a key role in maintaining healthy immune processes, seeming to protect against diseases such as type 2 diabetes and inflammatory bowel disease and make cancer cells more responsive to immune checkpoint therapies. Until the current work, though, no one could confirm the connection by showing how. Start to finish The researchers show in a report published July 27 in Naturethat the links begin with a lipid -- a fat -- in A. muciniphila's cell membrane. "That discovery was quite surprising. The usual suspects for triggering an immune response would be a protein or a sugar," said Clardy. After discovering the molecular structure of the lipid, the team found that it communicates with a pair of receptors on the surface of many immune cells. These receptors, known as toll-like receptor 2 and toll-like receptor 1, detect bacteria and help the immune system determine whether they're friend or foe. In this case, versions of TLR2 and TLR1 bound together in a way scientists hadn't seen before. The researchers showed in cell cultures that the fat's activation of TLR2-TLR1 can trigger the release of certain cytokines -- immune proteins involved in inflammation -- while leaving other cytokines alone. They also confirmed that the lipid helps maintain immune homeostasis. They found that low doses of the lipid act like a leash, preventing the immune system from reacting to a potentially harmful molecule until that molecule reaches significant levels. On the other end, they saw that high doses of the lipid don't stimulate an immune response much more than low or medium doses, keeping a healthy ceiling on inflammation. New doors open The work introduces new possibilities for developing drugs that piggyback on A. muciniphila's ability to manipulate the immune system and fight disease. Members of Clardy's lab have made that job easier by revealing the molecular structure of the lipid and figuring out how scientists can make it and similar ones easily in the lab. The study also provides a model for pinpointing how other members of the gut microbiome act on the body. "You can change the bacterium and apply the same set of tests," said Clardy. The researchers showed that, contrary to the expectations of many people in the field, such work doesn't require fancy techniques. They used traditional methods called spectroscopic analysis and chemical synthesis to find and understand the lipid molecule. In fact, despite its "remarkable activity," the lipid has a "generic structure" that would have flown under the radar of more advanced genomic or metabolomic analyses, Clardy said. "The gut microbiome and the immune system are very complicated, which makes you expect that answers will be complicated too," he said. "But sometimes complicated things are just lots of simple things." The findings arose from expertise across several disciplines. The team's work combined chemistry, structural biology, and pharmacology, specialties of Clardy's lab, with biological and immune analyses, strengths of Xavier's lab. Working on a project that's rooted in basic biochemistry and has immediate ties to human health "feels great," said Clardy. "In principle, this kind of work is what we're supposed to do, but it's not always the way things work out." "I was delighted to work with Ramnik, whom my mother would have called a 'real doctor,' on problems important to human diseases and unmet medical needs," he added. Funding and authorship Co-first authors are Munhyung Bae and Chelsi Cassilly, who conducted the work as postdoctoral fellows in the Clardy lab. Bae is now at Gachon University in South Korea and Cassilly is at the NASA Marshall Space Flight Center. Other authors are Xiaoxi Liu, formerly of HMS and Dana-Farber Cancer Institute; Sung-Moo Park, Betsabeh Khoramian Tusi, Xiangjun Chen, and Daniel Graham of the Broad Institute and Mass General; Jaeyoung Kwon, formerly of HMS and now at the Korea Institute of Science and Technology; Pavel Filipčík of the University of Otago in New Zealand and the HMS SBGrid Consortium; Andrew Bolze, Zehua Liu, and Hera Vlamakis of the Broad Institute; and Sara Buhrlage, associate professor of biological chemistry and molecular pharmacology at HMS and Dana-Farber. This work was funded by the National Institutes of Health (grants R01AT009708, P30DK043351, RC2DK114784, and F32AT010415) and the Linde Family Programme in Cancer Chemical Biology.