撰文丨王聪 编辑丨王多鱼 排版丨水成文 CAR-T 细胞疗法 是癌症治疗领域的一项重大突破，也是基因工程细胞作为治疗手段的有力证明。除了已 获批准用于白血病等血液类癌症治疗以外，CAR-T 细胞疗法还在实体瘤、自身免疫疾病以及组织再生方面 也展现出巨大潜力。 然而，大量临床试验显示，CAR-T 细胞疗法的效果仍面临着重大障碍，包括 T 细胞适应性和增殖能力有 限、癌症预处理患者的自体 T 细胞数量不足、慢性 CAR 刺激导致 T 细胞耗竭、患者体内的免疫抑制和营 养匮乏的肿瘤环境，以及 CAR-T 细胞通过胞啃作用从靶细胞获取抗原时发生自相残杀等。 CRISPR 基因编辑技术能够通过敲除特定基因，提高 CAR-T 细胞疗法的癌症治疗效果，但之前的研究通常 是在体外进行测试。 而最近，国际顶尖学术期刊 Nature 背靠背发表了两篇研究论文， 这两项研究利用 CRISPR 筛选和大规模 体内验证，评估了 CRISPR 筛选到的基因在敲除后是否能够通过增强 CAR-T 细胞的增殖和持久性来提高 癌症免疫治疗效果。 这项 研究来自奥地利科学院分子医学研究中心，论文题为： Systematic discovery o ...

Core Insights - CRISPR technology represents a revolutionary gene-editing method that offers unprecedented hope for treating genetic disorders, cancer, and rare diseases by precisely modifying disease-causing genes [1] - A significant breakthrough has been achieved by a team from Northwestern University, which has developed a new delivery system for CRISPR tools, enhancing efficiency and safety in gene therapy applications [1][3] Delivery Mechanisms - Current methods for delivering CRISPR into cells primarily rely on modified viruses and lipid nanoparticles (LNPs), each with distinct limitations [2] - Modified viruses are efficient at entering cells but pose safety risks due to immune responses and limited cargo capacity [2] - LNPs are safer but have low delivery efficiency, often getting trapped in cellular compartments, which hinders the effectiveness of gene tools [2] New Delivery System - The new system, termed "Lipid Nanoparticle Spherical Nucleic Acids" (LNP-SNA), features a special DNA shell that enhances visibility and acceptance by cells, significantly improving delivery efficiency [3] - This innovative delivery vehicle has been shown to enter cells over three times more efficiently than traditional lipid particles, with reduced toxicity and a threefold increase in successful gene editing probability [3] - The accuracy of gene repair has improved by over 60%, which is crucial for minimizing health risks associated with erroneous edits [3] Versatility and Future Applications - The LNP-SNA technology is modular, allowing for tailored delivery to specific cell types, such as liver, brain, or cancer cells, enhancing precision in treatment [4] - This new system has demonstrated excellent delivery results across various human cell types, including skin, immune, kidney, and bone marrow stem cells [4] - Seven drugs based on similar spherical nucleic acid technology are currently in human clinical trials, with some targeting cancer treatment [4] - The advancement in delivery mechanisms is critical for the future of gene editing therapies, potentially enabling the treatment of previously untreatable diseases [4]

Quantum Computing - Tsinghua and Peking University research teams have made significant progress in quantum computing architecture by implementing the AshN instruction set architecture, which supports direct programming of arbitrary two-qubit gates [1] - The quantum computing industry is transitioning from laboratory experiments to industrial applications, driven by technological breakthroughs, policy support, and market demand, with a projected market size of hundreds of billions by 2025-2030 [1] Refrigerants - The Ministry of Ecology and Environment has proposed a ban on the production of household refrigerators and freezers using hydrofluorocarbons (HFCs) as refrigerants starting January 1, 2026, marking a shift towards environmentally friendly refrigerants in China's home appliance industry [2] - The ban is expected to accelerate the transition to fourth-generation eco-friendly refrigerants, with natural refrigerants like R290 (propane) and R600a (isobutane) gaining traction, projected to reach 30% and 15% market share in commercial freezers by 2025, respectively [2] Gene Editing - A clinical trial has successfully demonstrated the use of gene editing technology to restore insulin production in a patient with type 1 diabetes, indicating a potential shift in diabetes management [3] - The rapid development of gene editing technologies, particularly CRISPR, is expanding the range of treatable conditions, with over 6,000 diseases now considered for gene therapy applications [3] Commercial Space - The commercial space industry in China is projected to grow from over 1 trillion yuan in 2020 to 2.3 trillion yuan by 2024, with a compound annual growth rate of approximately 22% [4] - Recent successful launches of low-orbit satellites indicate accelerated development in satellite internet infrastructure, with significant investment opportunities emerging in the commercial space sector [4] Artificial Intelligence in Biomanufacturing - The Ministry of Industry and Information Technology has released a notice to promote the integration of artificial intelligence in biomanufacturing, aiming to enhance the entire industry chain [5] Medical Advertising Regulation - New guidelines have been issued to clarify the definition of medical advertising and restrict its publication to licensed medical institutions, aiming to combat misleading advertisements [5] Virtual Power Plants - Guangzhou's plan for virtual power plants aims to achieve a capacity of 500,000 kilowatts by the end of 2027, with annual financial support of up to 10 million yuan for applications [6] Carbon Emission Financing - Guangdong has introduced a system to provide judicial support for carbon emission quota pledge financing, marking a first in the nation [7] Satellite Internet Development - The CCF and GuoShun Quantum have initiated a collaboration plan focusing on superconducting quantum computing, aiming to address key challenges in the field [7] Electronic Industry Trends - The global electronics market is expected to show divergence by 2025, with data center demand driving growth, while traditional consumer electronics face challenges due to inflation and lack of innovation [8]

Core Viewpoint - Gene editing technology is revolutionizing the understanding of life by allowing precise modifications of genetic sequences, akin to using a "molecular scissors" to correct genetic errors [2][3][4] Group 1: Technology Development - The evolution of gene editing technology has progressed rapidly, particularly with the advent of CRISPR technology in 2012, which significantly lowered the technical barriers and costs associated with gene editing [4][5] - Newer techniques such as base editing and guided editing have emerged, providing more precise tools for genetic modifications, enhancing both basic scientific research and translational medicine [5][6] Group 2: Applications in Medicine - Gene editing technology offers innovative treatment methods for genetic diseases, such as using CRISPR to edit hematopoietic stem cells for conditions like thalassemia, leading to significant symptom relief in patients [6] - In cancer treatment, gene editing is utilized in CAR-T therapy, which modifies patients' immune cells to better target and combat cancer cells [6] Group 3: Applications in Agriculture and Bio-manufacturing - In agriculture, gene editing has been used to develop new rice varieties that are resistant to diseases and environmental stressors, contributing to global food security [6] - The technology also plays a crucial role in bio-manufacturing, enhancing the efficiency of biofuel production and reducing costs in the synthesis of scarce drugs [6] Group 4: Ethical Considerations - The advancement of gene editing technology raises significant ethical concerns, particularly regarding the editing of human germline cells, which could permanently alter the human gene pool and pose risks to future generations [7][8] - There is a need for strict ethical guidelines and international collaboration to ensure responsible use of gene editing technologies, prioritizing non-heritable somatic cell editing for therapeutic purposes [7][8] Group 5: Regulatory Framework - In July 2024, the Ministry of Science and Technology released ethical guidelines for human genome editing research, addressing the ethical challenges and promoting healthy development in this field [8]

Core Viewpoint - The recent successful application of personalized gene editing therapy on a 6-month-old infant marks a significant milestone in the treatment of genetic diseases, opening new avenues for patients lacking effective treatment options [1] Group 1: Gene Editing Technology Overview - Gene editing technology allows for precise deletion, insertion, or replacement of specific genes, akin to a "molecular scissors" that can correct and modify defective genes [2][4] - Unlike transgenic technology, which randomly integrates foreign genes into an organism's genome, gene editing modifies the organism's own genes without disrupting the overall structure [2][4] - The evolution of gene editing technology has progressed rapidly, particularly since the advent of CRISPR technology in 2012, which has simplified the process and significantly reduced costs [5][6] Group 2: Applications in Medicine - Gene editing technology is being applied in the treatment of genetic diseases, such as thalassemia, where CRISPR can edit a patient's hematopoietic stem cells to restore normal gene expression [7] - In cancer treatment, CAR-T therapy utilizes gene editing to enhance the immune cells' ability to combat cancer cells, demonstrating the technology's potential in oncology [7] - The technology also aids in modeling complex diseases in research, accelerating drug development by allowing scientists to observe disease progression in genetically edited organisms [7] Group 3: Applications in Agriculture and Bio-manufacturing - In agriculture, gene editing has led to the development of new rice varieties that are resistant to diseases and environmental stress, contributing to global food security [8] - In bio-manufacturing, gene editing enhances production efficiency and reduces costs, such as in the production of biofuels and scarce pharmaceuticals [8] Group 4: Ethical Considerations - The advancement of gene editing technology raises ethical concerns, particularly regarding the editing of human germline cells, which could permanently alter the human gene pool [10] - Ethical guidelines emphasize the importance of prioritizing non-heritable somatic cell editing for therapeutic purposes and prohibiting germline editing in clinical applications [10][11] - The establishment of strict technical boundaries and international regulatory frameworks is essential to prevent ethical violations and ensure that gene editing serves societal welfare [10][11]

Core Insights - A rare disease case involving a baby named KJ Malden has shown promising results from a custom gene editing therapy, marking a potential breakthrough for treating rare genetic disorders [1][2] - The therapy utilized CRISPR technology to correct a genetic mutation causing CPS1 deficiency, a condition with high mortality rates and typically requiring liver transplants for treatment [1][3] Group 1: Treatment Details - KJ Malden, diagnosed with CPS1 deficiency shortly after birth, received the world's first custom gene editing therapy starting in February [1][2] - The treatment involved three intravenous infusions over several months, where lipid nanoparticles delivered "molecular scissors" to correct the mutation in liver cells [2] - Following the treatment, Malden has shown significant improvement, being able to consume a protein-rich diet and recover quickly from minor illnesses [2] Group 2: Industry Context - Approximately 350 million people worldwide suffer from rare diseases, many of which are caused by genetic mutations [3] - The CRISPR gene editing technology, which emerged in 2012, has gained recognition for its precision and efficiency, receiving the Nobel Prize in Chemistry in 2020 [3] - This case represents a significant step in applying gene editing technology to treat various rare diseases, with ongoing observation required to assess long-term effects [2][3]