瑞·达利欧：AI将影响方方面面。图片来源：Jemal Countess/Getty Images for TIME 瑞・达利欧（ Ray Dalio ）是一位作家、全球经济学家，也是全球最大对冲基金桥水联合基金（ Bridgewater Associates ）的创始人、首席投资官导师。 译者：朴成奎 在财富Plus，网友们对这篇文章发表了许多有深度和思想的观点。一起来看看吧。也欢迎你加入我们，谈谈你的 想法。今日其他热议话题： 在我看来，我们已经到达了一个新时代的边缘。在这个新时代，机器思维将在很多方面补充甚至超越人 类思维，就像在工业时代，机器补充甚至超越了人类的劳动力那样。随着计算工具的发明，靠人脑来进 行数学运算和存储记忆的重要性变得大大降低。现在我们查找信息会用谷歌这种搜索引擎，而不是用更 传统的方式。同样，或许用不了多久，当我们在各种情境下需要进行理性决策时，我们也会寻求计算机 的指引，因为它能给出比我们自己的大脑更快、更好的指导。 未来五年，我们将会见证大多数领域的显著进步。创造AI只是应用AI的第一步。我和桥水公司专业从 事AI投资已经有几十年了，我们现在正在发掘的机会，在普通人看来简直难以置 ...

Summary of GeneDx Conference Call Company Overview - GeneDx was established 25 years ago at the National Institutes of Health, focusing on diagnosing difficult cases, particularly in rare diseases [4][5] - The company has built the largest rare disease data asset in the U.S., with over 800,000 exomes and genomes and more than 6,100,000 phenotypic data points [5][6] Strategic Initiatives - GeneDx aims to reduce the diagnostic odyssey, which currently takes about five years, to weeks or even hours [5][6] - The company is focusing on increasing utilization in pediatric outpatient settings and NICUs [6] Differentiation and Market Position - GeneDx's tests are differentiated by their extensive data assets, which include a highly representative database and a robust phenotypic data set [7][8] - Approximately 60% of the time, both parents are tested, enhancing the accuracy of diagnoses [7] - The company claims an 80% market share among expert geneticists, with significant growth potential in pediatric neurology and NICU settings [14][16] Market Penetration - In pediatric neurology, GeneDx has only penetrated about 14% of the patient population, indicating substantial growth opportunities [16] - In NICUs, fewer than 5% of babies currently receive genetic testing, despite studies showing that 60% would benefit from it [19][22] - GeneDx aims to increase its NICU testing to approximately 225,000 tests annually, targeting a quarter million children by 2026-2027 [24] Product Development and Testing - GeneDx has launched a two-day ultra-rapid turnaround time for genome testing, which is expected to enhance market uptake [25][26] - The company is expanding its testing indications to include conditions like cerebral palsy and hearing loss, focusing on the best clinical outcomes [29][30] Financial Performance and Cost Management - GeneDx has achieved profitability and aims for continued profitable growth, focusing on areas with sufficient reimbursement [17][18] - The company has reduced denial rates from 65% to less than 50% for pediatric neurologists, improving reimbursement rates and gross margins [48][49] - Current gross margins for exome and genome testing are around 80%, with ongoing efforts to reduce costs further through automation and technology [54][56] Future Growth and Market Strategy - GeneDx plans to expand into adult genetic testing as reimbursement pathways develop, aiming for early diagnosis across all age groups [62][63] - The company is also exploring monetization of its extensive data set for biopharma, aiming to contribute to drug discovery and clinical trial development [64][66] Conclusion - GeneDx is positioned as a leader in genetic testing for rare diseases, with a strong focus on data-driven diagnostics and expanding market opportunities in pediatric and adult settings. The company is committed to improving patient outcomes through faster and more accurate testing while maintaining a focus on profitability and cost management.

Core Viewpoint - The article highlights the significant contributions of Huang Zhiwei, a returning scientist, in advancing basic research in life sciences at Harbin Institute of Technology, emphasizing the importance of foundational research for achieving high-level technological self-reliance and building a world-class scientific power [1][4]. Group 1: Research Achievements - Huang Zhiwei established a laboratory from scratch at Harbin Institute of Technology in 2012, focusing on basic research in immunology and infectious diseases [1]. - In 2014, his team discovered the structure of the HIV virus virulence factor, which had been elusive for over 30 years, providing a foundation for developing anti-HIV drugs [2]. - The research findings were published in the journal "Nature," attracting international attention and collaboration [2]. Group 2: Research Environment and Philosophy - Huang Zhiwei created a supportive research environment at the Life Sciences Center, allowing researchers to explore innovative ideas freely [3]. - He emphasizes the importance of hands-on involvement in experiments and meticulous record-keeping to ensure reproducibility and high-quality research outcomes [2][3]. - The center has produced significant breakthroughs in gene editing and metabolic disease mechanisms, establishing a competitive research platform internationally [3]. Group 3: Future Aspirations - Huang Zhiwei expresses a commitment to tackling unresolved scientific questions in life sciences, maintaining a beginner's mindset to explore frontiers and contribute to the field's advancement [4].

CRISPR-Cas 系统是存在于 原核生物 （ 细菌和古菌 ） 中的一类古老的免疫系统，用于抵御防御外源遗 传元件 （例如噬菌体） 入侵。通过对该系统的研究，科学家们开发出了一系列强大的基因编辑工具，例如 CRISPR-Cas9，其通过RNA引导的Cas9核酸酶，对DNA进行切割，实现基因组编辑。 编辑丨王多鱼 排版丨水成文 2025 年 5 月 20 日，西北农林科技大学 王小龙 团队与上海科技大学 吴兆韡 团队合作，在 Nature 子刊 Nature Chemical Biology 上 发 表 了 题 为 ： Engineering eukaryotic transposon-encoded Fanzor2 system for genome editing in mammals 的研究论文 【2】 。 2023 年 6 月， 张锋 团队在 Nature 期刊发表论文 【1】 ， 在 真核生物 中发现了第一个 RNA 引导的 DNA 切割酶—— Fanzor ，这种新型 CRISPR 样系统，可以在重编程后实现对人类基因组的编辑。 相比 CRISPR-Cas系统，Fanzor 系统非常紧凑，更容易递 ...

Financial Data and Key Metrics Changes - The company reported a solid financial position with $1.6 billion on the balance sheet, indicating strong capital efficiency and the ability to fund future projects [3][4]. Business Line Data and Key Metrics Changes - The approved product, Kasjevi, is now in eight different jurisdictions for treating sickle cell and beta thalassemia, with a revenue of $14 million generated from 90 cells collected and 65 ATCs as of Q1 [12][13][22]. - The company is targeting 75 ATCs to support the demand for Kasjevi, indicating a significant multi-billion dollar market opportunity [14][16]. Market Data and Key Metrics Changes - The company sees a substantial market in the Middle East, with over 23,000 patients identified in Gulf Coast countries, which is expected to play a significant role in Kasjevi's market expansion [16][17]. Company Strategy and Development Direction - The company aims to focus on transformative gene-based medicines while exploring opportunistic deals, such as the partnership with Sirius Therapeutics for an siRNA platform [4][8]. - The strategic approach includes a phase two trial for Factor XI, which is expected to provide immediate value-creating catalysts in the next 12 to 18 months [10][11]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the launch performance of Kasjevi and the potential for significant patient initiation growth, supported by manufacturing investments [13][14][22]. - The company is optimistic about the upcoming data readouts from various programs, including CTX 310, which showed promising early results with an 82% reduction in triglycerides and 81% reduction in LDL [6][28]. Other Important Information - The company is actively looking for business development opportunities in a buyer's market, with plans to explore partnerships that can create significant value [48][50]. - The cost of goods for new therapies is expected to be in the low five-figure range, allowing for competitive pricing against existing therapies [44][45]. Q&A Session Summary Question: What does the Sirius deal do for your platform with siRNAs? - The Sirius deal is seen as a diversification play, allowing the company to explore complementary assets in a buyer's market [8][9]. Question: How has the launch of Kasjevi been trending? - The launch has been successful, with significant revenue and patient initiation growth expected [12][13]. Question: What are the key days to watch for the Factor XI program? - The initiation of the TKA study in the second half of the year is a key milestone [11]. Question: How does the company plan to address the preconditioning regimen for Kasjevi? - The company is working on approaches to make the preconditioning regimen more comfortable for patients [23][25]. Question: What is the company's strategy for broad diseases versus rare diseases? - The company aims to ensure low production costs to remain competitive in both broad and rare disease markets [44][45].

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].

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]

定制基因编辑疗法治愈罕见遗传病患儿 智通财经5月16日电，美国费城儿童医院与宾夕法尼亚大学医学团队利用定制的CRISPR基因编辑疗法， 成功治愈了一名患有罕见遗传病的儿童。这项研究成果已发表在《新英格兰医学杂志》上，并在美国基 因与细胞治疗学会年会上进行了报告。该突破将为治疗目前尚无有效疗法的罕见疾病打开新的大门。 ...

Market Overview - The market experienced a weak fluctuation, with all three major indices closing down. The consumer sector showed resilience, while over 3,800 stocks declined [1][3] - Goldman Sachs raised the 12-month targets for the MSCI China Index and the CSI 300 Index to 84 points and 4,600 points, respectively, indicating potential upside of 11% and 17%. They maintain an overweight rating on Chinese stocks and suggest focusing on multiple themes for excess returns [1] Sector Performance - New hotspots emerged in the market, particularly in the ergot sulfur concept, with Chuaning Biological hitting a 20% limit up. Other sectors such as beauty care and medical aesthetics also saw significant gains [1] - The food and beverage sector rebounded in the afternoon, with several stocks, including Xiwang Food, hitting the limit up. The shipping and port sector continued its upward trend, with Nanjing Port achieving three consecutive limit ups [1] - The textile and apparel sector showed recovery, with Huafang Co. achieving six limit ups in eight days. Other sectors like coal, chemicals, synthetic biology, rare earths, and ST stocks also performed well [1] Individual Stock Movements - A total of 1,407 stocks rose, while 3,856 stocks fell, with 149 stocks remaining flat. There were 78 stocks hitting the limit up and 12 stocks hitting the limit down [3] - The Shanghai Composite Index fell by 0.68% to 3,380.82 points, with a trading volume of 461.3 billion yuan. The Shenzhen Component Index dropped by 1.62% to 10,186.45 points, with a trading volume of 688.7 billion yuan. The ChiNext Index decreased by 1.91% to 2,043.25 points [3] Fund Flow - Main funds focused on sectors such as chemical pharmaceuticals, small metals, and passenger vehicles, with notable net inflows into stocks like BYD, Chuaning Biological, and Shenghe Resources [4] Regulatory Developments - The China Securities Regulatory Commission (CSRC) is expediting the introduction of a comprehensive policy package to deepen reforms in the Sci-Tech Innovation Board and the ChiNext, aiming to enhance the inclusiveness and adaptability of the system [5] Industry Insights - The anti-aging industry is divided into medical and non-medical tracks, with the former focusing on basic medical research and the latter encompassing various fields such as sociology and artificial intelligence [2] - The China Academy of Sciences has made breakthroughs in the electro-catalytic reforming of waste plastic PET to produce biodegradable plastic PGA, with projected market demand reaching millions of tons [6] Economic Outlook - Analysts from Minsheng Securities suggest that China's asset resilience may be higher than that of overseas markets, with a focus on consumption sectors and undervalued financial stocks [9] - Huazhong Securities indicates that the market will continue to experience fluctuations until significant improvements in the macroeconomic fundamentals are observed [10]