Core Viewpoint - Prime Medicine has achieved a significant breakthrough in gene editing by using prime editing technology for the first time in human patients, marking a milestone in the field of biotechnology [1] Group 1: Company Developments - Prime Medicine announced the application of its prime editing therapy PM359, which aims to correct gene mutations causing chronic granulomatous disease [1] - The therapy has received initial clinical data supporting its safety and efficacy, indicating a promising advancement in treatment options for genetic disorders [1] Group 2: Industry Impact - The use of prime editing technology represents a major advancement in gene editing, potentially transforming treatment approaches for various genetic diseases [1] - Chronic granulomatous disease, which affects the functionality of immune cells including neutrophils, highlights the critical need for innovative therapies in the biotechnology sector [1]

Core Insights - The article discusses the advancements in gene editing technology, particularly focusing on the development of a new delivery system called ENVLPE, which enhances the efficiency and safety of gene editing tools [1][2][3]. Group 1: Gene Editing Technology - Gene editing technologies like CRISPR-Cas9 have revolutionized the field by allowing precise modifications of DNA, but challenges remain in delivering these tools effectively to target cells [1][3]. - New generation tools such as base editors and prime editors have emerged, offering safer and more precise modifications without cutting the DNA double strand [1]. Group 2: ENVLPE Delivery System - ENVLPE, which stands for "engineered nuclear cytoplasmic carrier for loading programmable editors," is a non-infectious viral-like particle designed to efficiently deliver gene editing tools to target cells [3][4]. - This system addresses two major limitations of earlier delivery systems: the instability of guide RNA payloads and the low packaging efficiency of functional gene editors in production cells [3][4]. Group 3: Practical Applications - In tests on genetically blind mice, the ENVLPE system successfully restored light response by repairing a mutation in the Rpe65 gene, demonstrating its therapeutic potential [5]. - Compared to existing delivery systems, ENVLPE showed superior performance, requiring over ten times less dosage to achieve similar therapeutic effects [5]. Group 4: Cancer Treatment Potential - ENVLPE also presents new possibilities for adoptive T cell therapy in cancer treatment by efficiently removing specific molecules from T cells that could trigger immune rejection when transplanted into non-donor recipients [6][7]. - This innovation could lead to the development of universal T cells, reducing treatment costs and increasing accessibility for cancer patients [7]. Group 5: Future Directions - Researchers are working to enhance the targeting precision of ENVLPE by integrating natural diversity resources and AI-assisted protein design technologies, aiming for a more specific and controllable delivery process [7]. - There is an active pursuit of funding and collaboration with pharmaceutical companies to optimize ENVLPE for various diseases, with the goal of advancing it towards clinical applications [7].

Group 1 - The first personalized CRISPR gene editing therapy has been developed and successfully applied to a patient with a rare genetic disease, marking a significant milestone in biotechnology [2] - The gene editing field is considered one of the forefront directions in biotechnology, with the potential for long-lasting effects from a single treatment [2] - The global gene editing market is projected to reach $36.061 billion by 2030 according to Statista [2] Group 2 - Xiaomi is set to release its self-developed mobile SoC chip named Xuanjie O1, which is expected to capitalize on the rapid development of AI technology [3] - The emergence of edge AI applications is anticipated to drive significant growth in the SoC market, with increasing demand for AI-enabled devices such as AI headphones and glasses [3] Group 3 - The first batch of unmanned logistics delivery vehicles has been officially put into operation, with potential cost reductions of up to 20 times for companies utilizing this technology [4] - The market potential for unmanned delivery vehicles is estimated to be between $468 billion and $728 billion, depending on the basis of calculation [4] Group 4 - Humanoid robots are seen as a key breakthrough in the integration of technology and healthcare, particularly in the context of an aging population [5] - The global population aged 60 and above is expected to reach 2.1 billion by 2050, increasing the demand for elder care solutions, including robotic assistance [5]

Core Viewpoint - The article discusses advancements in gene editing technology, specifically the development of EvoCAST, a highly efficient and precise system for gene insertion in human cells, which addresses the limitations of existing gene editing methods [2][3][10]. Group 1: Gene Editing Challenges - Integrating entire genes into specific genomic locations has been a long-standing challenge in the field of gene editing [2]. - Existing gene editing technologies can repair most pathogenic gene mutations, but the genetic diversity of many diseases necessitates multiple tailored therapies, limiting patient benefits [2]. Group 2: Discovery of CAST - In June 2019, the discovery of CRISPR-associated transposase (CAST) by teams led by Zhang Feng and Samuel Sternberg marked a significant advancement, allowing for the targeted integration of large DNA segments without causing double-strand breaks [2][3]. Group 3: Development of EvoCAST - The collaboration between Liu Ruqian and Samuel Sternberg led to the evolution of EvoCAST, which significantly enhances the activity of CAST, achieving a 420-fold increase in efficiency for gene insertion in human cells [3][7]. - EvoCAST supports the integration of DNA segments larger than 10kb and can mediate the insertion of therapeutic payloads at various genomic loci related to diseases [3][7]. Group 4: PACE Technology - The PACE (Phage-Assisted Continuous Evolution) technology was utilized to improve the activity of CAST, simulating natural selection to evolve the transposase [5][6]. - After hundreds of rounds of evolution, a variant of the TnsB protein was developed, enhancing integration activity over 200 times without the need for toxic bacterial proteins [6]. Group 5: Comparative Analysis with eePASSIGE - EvoCAST and eePASSIGE, another system developed using PACE, have complementary advantages; eePASSIGE offers higher efficiency, while EvoCAST provides greater editing purity [9][10]. - EvoCAST operates in a single step for gene integration, making it simpler compared to the two-step process required by eePASSIGE [9]. Group 6: Implications for Future Research - The research establishes CAST as a powerful platform for RNA-guided gene integration, suitable for various applications in life sciences and disease treatment [10]. - The study demonstrates how laboratory evolution can transform natural systems into effective therapeutic tools, providing new strategies for improving other CAST systems for efficient gene editing [10].

（原标题：突发，白宫坐不住了，美国痛失3A评级！基因编辑新突破，治愈罕见遗传病） 科学家用基因编辑成功治愈罕见遗传病。 穆迪下调美国主权信用评级 据新华社，当地时间5月16日，国际信用评级机构穆迪公司宣布，由于美国政府债务及利息支出增加，该机构决定将美国主权信用评级从Aaa下调 至Aa1，同时将其评级展望从"负面"调整为"稳定"。 穆迪发布公告说，评级下调反映出过去十多年来美国政府债务和利息支付比例升至显著高于拥有类似评级国家的水平。穆迪认为，持续的大规模 财政赤字将进一步推高政府债务和利息支出负担。与美国以往以及其他高评级主权国家相比，美国财政状况很可能会恶化。 对此，美国白宫批评国际信用评级机构穆迪当天下调美国主权信用评级的决定，称其为"政治决定"。白宫副新闻秘书库什·德赛在一份新闻稿中指 出："如果穆迪还有信誉，他们就不会在过去四年的金融灾难发生时保持沉默。" 白宫还将矛头指向之前的拜登政府，白宫发言人表示，"特朗普政府和共和党正致力于解决拜登留下的烂摊子，削减政府中的浪费、欺诈和滥用职 权……" 对此，美国民主党领袖舒默则称，穆迪此举"应该为特朗普和国会共和党人敲响警钟，让他们停止不计后果地推行赤字减 ...

Core Viewpoint - The recent birth of genetically modified wolf pups, resembling the extinct dire wolf, marks a significant achievement in de-extinction technology, raising questions about the implications of reviving extinct species and the intersection of science and ethics [7][9][13]. Group 1: Scientific Achievement - Colossal Biosciences announced the successful revival of the dire wolf, claiming it as the first case of resurrecting an extinct animal through ancient DNA extraction and gene editing [9][11]. - The dire wolf's genome was compared with that of modern gray wolves, revealing a 99.3% similarity, with 80 key gene differences identified [11][13]. - Using CRISPR technology, 14 genes in gray wolf embryos were modified to incorporate traits typical of the dire wolf, leading to the birth of three pups in 2024 and 2025 [11][13]. Group 2: Controversy and Definition - There is debate within the scientific community regarding the definition of "revival," with some experts arguing that the modified wolves are more like hybrid wolves than true dire wolves, as 99.9% of their genome remains gray wolf [13][15]. - Critics emphasize that true revival of extinct species may be impossible due to the degradation of ancient DNA, which complicates the cloning process [15][20]. Group 3: Ethical and Ecological Considerations - The project raises ethical questions about humanity's right to alter natural evolutionary processes and the potential ecological impacts of introducing modified species into existing ecosystems [20][21]. - Concerns exist regarding the unforeseen consequences of releasing genetically modified organisms into the wild, with experts warning of potential ecological disruptions [20][21]. - Colossal Biosciences aims to create "functional replicas" of extinct species to restore ecological functions and enhance biodiversity, rather than achieving a perfect genetic replica [15][20]. Group 4: Future Aspirations and Challenges - Colossal Biosciences has plans to revive other extinct species, such as the woolly mammoth and the dodo, with the goal of promoting vegetation recovery in the Arctic tundra to combat climate change [16][18]. - The company has already made strides in mammoth DNA replication, although experts caution that these efforts may be overstated and not fully representative of the original species [18][20]. - The challenges of reviving extinct species include the need for intact DNA, successful embryo development, and appropriate environmental conditions for rearing the animals [21][26].

于全球率先实现了大片段DNA精准插入技术。 本文为IPO早知道原创 作者｜C叔 微信公众号｜ipozaozhidao 据IPO早知道消息，近日，苏州齐禾生科生物科技有限公司（下称"齐禾生科"）完成超2亿元人民币 A轮融资。本次融资由知名基金和老股东共同投资，凯乘资本将继续助力后续A+轮融资。所筹资金将 主要用于公司基因编辑技术的深度研发、基因编辑产品管线的优化与拓展、及商业化平台落地，进一 步提升公司在生物技术产业领域的核心竞争力与市场影响力。 齐禾生科创立于2021年，专注于开发自主可控新型基因编辑技术、创制卓越生物性状和产品。成立 后，公司在基因编辑新工具挖掘、自主知识产权基因编辑工具优化、安全高效递送系统开发和突破性 种质资源创制等多方面均取得显著进展，构建了以SEEDIT™平台为核心的全链条技术平台，商业化 进程位居行业前沿，获2张安全证书，且成为首个获美国USDA豁免的中国企业。 齐禾生科以国家战略需求为导向，目前已经建立起了全球领先的独立自主可控的基因编辑技术体系。 在核酸酶、碱基编辑和引导编辑的基础上，公司在全球率先实现了大片段DNA精准插入技术，为基 于基因堆叠的生物育种和植物合成生物制造产业 ...