2024年度上海市科学技术奖 0 1 地贫基因疗法： "一次治疗，终身治愈" 邦耀生物 项目团队作为国内最早开展 CRISPR-Cas9 基因编辑技术的科研团队，早于2013 年在 Nature Biotechnology 期刊 发文报道了 全球首次将 CRISPR-Cas9 成功应用于哺乳动物基因编辑 。多年来依托核 心的基因编辑技术，以 β-地中海贫血 （地贫） 等单基因血液遗传病为重点，项目团队开发了首款地贫基因 疗法。 刘明耀教授（左1）、杜冰（左2）教授代表团队领取荣誉 "上海市科学技术进步奖" 是上海科技领域的最高荣誉之一，旨在表彰在科学技术研究、技术开发与创新、成 果转化和高新技术产业化中取得重大突破或作出突出贡献的个人与组织。该奖项评选标准严格，不仅注重技术 的先进性和创新性，更强调其实际应用价值、产业带动能力以及对经济社会发展的实际贡献。荣获一等奖的项 目代表其在所属领域达到了国际先进或国内领先水平，是具有显著的社会效益或经济效益的重大科技成果，含 金量备受认可。 本次获奖，标志着 邦耀生物 在前沿生物医药技术领域的创新能力和转化成果获得了政府与学术界的双重肯 定。 作为获奖项目的核心完成单 ...

Core Viewpoint - The article highlights the significant breakthrough in gene editing therapy for β-thalassemia, particularly through the case of a patient named "Xixi," who was successfully treated using CRISPR technology, marking a milestone in the treatment of hereditary blood disorders [1][4]. Group 1: Patient Case Study - Xixi, diagnosed with the most severe form of β0/β0 thalassemia at 9 months old, required lifelong blood transfusions and iron removal therapy, placing a heavy burden on his family [3]. - In 2020, at the age of 7, Xixi became the first patient globally to receive CRISPR gene editing therapy (BRL-101) and successfully became independent from blood transfusions just 56 days post-treatment [6]. - Five years later, Xixi has maintained his health without transfusions, with hemoglobin levels around 140g/L, showcasing the long-term efficacy and safety of the treatment [6][10]. Group 2: Scientific Breakthrough - β-thalassemia is a hereditary blood disorder caused by defects in the globin gene, traditionally treated through costly and complex allogeneic stem cell transplants, which carry high risks [10]. - The BRL-101 gene therapy utilizes CRISPR technology to modify the BCL11A locus in the patient's hematopoietic stem cells, allowing for a one-time treatment that can potentially cure the disease [10]. - The therapy's delivery method avoids safety issues associated with viral vectors, enhancing its safety profile [10]. Group 3: Company Development and Achievements - Shanghai Bangyao Biotechnology has been deeply involved in gene therapy, with BRL-101 receiving IND approval in August 2022 and achieving significant clinical milestones since its inception [14]. - The company has published influential research in top journals and has been recognized at major international conferences, receiving awards for its contributions to rare disease treatment [15]. - Future plans include exploring treatments for sickle cell disease (BRL-102) and expanding global clinical collaborations to benefit patients with various hereditary blood disorders [14][17].

Group 1: Industry Overview - The new gene editing technology developed by the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences allows precise manipulation of large DNA segments ranging from thousands to millions of bases, significantly enhancing the scale and capability of gene editing [1] - The gene editing market is projected to reach an annual revenue of $30 billion by 2030, indicating a strong growth trajectory [2] - Gene editing technology is transitioning from theoretical research to practical applications, with significant implications in medicine for treating genetic diseases and in agriculture for developing new crop varieties [2] Group 2: Company Developments - Approximately 20 listed companies in the A-share market are involved in gene editing technology [3] - A company has established a cotton research institute in collaboration with Huazhong Agricultural University, utilizing gene editing and hybridization techniques for cotton seed development [3] - Another company is conducting research on the water buffalo genome and has developed a breeding model based on whole genome data analysis to enhance breeding efficiency [3] - A biotechnology company focuses on providing gene-modified animal models and related technical services for drug development and disease research, having developed over 21,000 models by the end of 2024 [3] - Beijing Baipu Sais Biotechnology Co., Ltd. has launched CAS series proteins for targeted gene editing applications [4]

Core Viewpoint - The research team from Uppsala University in Sweden has successfully demonstrated the survival and functionality of donor pancreatic β cells obtained through CRISPR-Cas gene editing technology in a type 1 diabetes patient for 12 weeks without the use of immunosuppressants, indicating a potential breakthrough in curing type 1 diabetes [1] Industry Summary - Over 20 listed companies in the A-share market are involved in gene editing technology [1] - According to data from Zhitongcaijing, a total of 21 gene editing concept stocks have received "positive" ratings from institutions, including buy, increase, and strong recommendation ratings [1] - Among these, Shenguan Medical (300888) is the most favored by institutions, with 27 institutional research reports mentioning this stock [1]

Core Viewpoint - The research team from Uppsala University has successfully demonstrated the world's first instance of donor pancreatic β cells edited by CRISPR-Cas technology surviving and functioning for 12 weeks in a type 1 diabetes patient without the use of immunosuppressants, offering hope for a potential cure for the disease [1][2]. Group 1: Research Breakthrough - The study utilized CRISPR-Cas12b technology to modify donor pancreatic cells by knocking out B2M and CIITA genes to reduce immunogenicity and overexpressing CD47 through lentiviral transduction [1]. - The modified low-immunogenicity cells were implanted into a 42-year-old subject's left brachioradialis muscle, with the entire procedure conducted without glucocorticoids, anti-inflammatory drugs, or immunosuppressants [1]. Group 2: Clinical Outcomes - Monitoring over 84 days showed that the transplanted cells successfully evaded the immune system, with no T cell activation or antibody response observed [2]. - Imaging confirmed the good survival of the graft, and the patient's hemoglobin A1c levels significantly decreased by 42% [2]. - Although the number of transplanted cells was only 7% of what is needed for treatment, this experiment marks a critical breakthrough in demonstrating survival and functionality [2]. Group 3: Future Implications - The low-immunogenic gene editing technology used in this study may lead to the development of more curative β cells, potentially allowing for a diabetes cure without the need for immunosuppression [2]. - This advancement could relieve millions of patients from the daily pain of injections and the long-term complications associated with diabetes [2].

Core Viewpoint - The article discusses the current state of the US stock market, highlighting a bullish sentiment driven by factors such as corporate buybacks, retail investor activity, and strong capital flows, while also addressing potential risks of a market correction in the near future [4][12][39]. Group 1: Market Sentiment and Predictions - Scott Rubner from Citadel Securities believes the bull market has not peaked yet, with a positive outlook for the next month due to corporate buybacks, continued retail buying, and ample institutional holdings [6][9]. - Historical data shows that July has been the best month for the S&P 500 since 1928, while September tends to be weaker, suggesting a favorable environment for stocks in July [9]. - Retail investors have been net buyers for 14 consecutive trading days, marking the longest streak since December of the previous year, with their holdings reaching 20% of the market [9][18]. Group 2: Corporate Buybacks and Retail Investor Activity - Corporate buybacks are expected to reach $1 trillion by 2025, with a significant increase in buyback activity anticipated after August, providing strong support for stock prices [9][21]. - The summer months are traditionally a peak period for corporate buybacks, which will likely contribute to demand in the market [21]. - Retail investors have contributed significantly to market momentum, with net inflows of $155 billion into stocks and ETFs this year, representing nearly 60% of household financial assets when including indirect holdings [18][39]. Group 3: Diverging Views Among Analysts - Michael Hartnett from Bank of America warns of increased short-term correction risks, citing that all sell signals have been triggered and the market is entering a "danger zone" [12][14]. - Hartnett highlights a concerning concentration of market strength among a few tech giants, which could lead to volatility if economic or policy conditions change [14][25]. - The current market breadth is insufficient, with a significant disparity between large-cap tech stocks and small-cap/value stocks, reminiscent of the 2000 tech bubble [25]. Group 4: Sector Focus and Investment Opportunities - The AI sector remains a hot topic, with major companies like NVIDIA, Microsoft, and Tesla expected to drive technological innovation in the second half of the year [31]. - The pharmaceutical and biotech sectors are also gaining attention, particularly gene editing technologies like CRISPR, which are seen as promising for extending human lifespan [34]. - Investors are advised to focus on innovation pipelines and core product launches while being cautious of high volatility and speculative growth stories in the biotech space [37]. Group 5: Overall Market Outlook - The US stock market is expected to maintain a strong rebound in the short term, with structural opportunities present, particularly in tech and biotech sectors [39]. - However, investors should remain vigilant for potential corrections as market sentiment heats up, with recommendations to increase hedging strategies as September approaches [39][42]. - The article emphasizes the importance of balancing aggressive investment strategies with profit protection to navigate the market effectively [42].

Summary of Key Points from the Conference Call Industry Overview - The conference call discusses the **global and Chinese laboratory animal market**, highlighting a pre-pandemic growth rate of **5%-7%** globally, with China reaching **15%-20%**. Post-pandemic, China's growth has slowed to **5%-7%** primarily due to price increases, not volume changes. The domestic market size is approximately **40 billion RMB**, with ancillary services generating around **20 billion RMB** in revenue [1][2]. Core Insights and Arguments - **Price Increases**: The rise in laboratory animal prices is attributed to multiple factors, including increasing labor, feed, energy costs, and testing fees [4]. - **Market Dynamics**: If internal demand from pharmaceutical companies is included, the overall market space would significantly expand, although specific data is currently unavailable [5]. - **Outsourcing Trends**: Pharmaceutical companies are reducing outsourcing to cut costs but are increasingly adopting one-stop services to enhance R&D efficiency. Many firms are opting for phased outsourcing, keeping early research in-house while outsourcing evaluation stages to ensure objectivity [6]. - **Market Leaders**: In the U.S., key players include **Jackson Laboratory**, **Charles River Laboratories**, and **Taconic Biosciences**, each with distinct market strategies and growth trajectories [7][8]. - **Regulatory Impact**: New U.S. policies from **FDA** and **NIH** limiting animal use may lead to a contraction in the U.S. market, shifting focus towards cell or organoid projects [10]. Additional Important Content - **European Market**: The European laboratory animal industry is fragmented, with strict animal welfare regulations leading to a shift towards cell-based alternatives [9]. - **Gene Editing Technologies**: The conference highlights the dominance of **CRISPR/Cas9** technology in gene editing, with companies like **百奥** and **博** leading in humanized antibody mouse technology [3][14]. - **Market Trends**: Demand for laboratory animals is increasing from pharmaceutical companies, with a **10%** year-on-year sales growth noted, particularly for specific strains like **C57** and **SD rats** [21]. - **CRO Challenges**: The decline in orders from Contract Research Organizations (CROs) is linked to U.S. government restrictions on using Chinese CROs, leading to a shift in orders to South Korea and Japan [22]. - **Future Directions**: The laboratory animal industry is expected to consolidate, with smaller companies potentially being acquired by larger firms, emphasizing the importance of scale in reducing costs [28][29]. - **Emerging Research Areas**: While tumor immunology has been a focus, research into metabolic diseases is gaining traction, indicating a shift in research priorities [30]. Conclusion The laboratory animal market is experiencing significant changes driven by regulatory shifts, cost pressures, and evolving research needs. The consolidation trend suggests that larger firms will dominate, while emerging areas of research may redefine market dynamics in the coming years.

Core Insights - The pearl farming industry in China, as the world's largest freshwater pearl producer, is entering a critical phase of transformation and upgrading after decades of rapid development [1][10] - The import and export data of cultivated pearls in China shows a pattern of "import contraction and export expansion," with significant changes in both volume and value [12][14] Industry Overview - Cultivated pearls are formed through artificial intervention in bivalve mollusks, with a core made of implanted materials, primarily composed of calcite [2] - The cultivation cycle for freshwater pearls is typically 2-4 years, while seawater pearls take longer, around 3-5 years [2] Industry Development History - The industry has gone through four main stages: the embryonic stage before 1958, the scale development stage from 1958 to 1977, the industrial upgrading stage from 1978 to 2000, and the modernization and transformation stage from 2000 to present [4][5][6] Current Industry Status - In 2022, China's freshwater pearl production reached 697.39 tons, accounting for over 95% of global production, with major production areas in Zhejiang, Jiangsu, and Anhui [10] - The export volume of cultivated pearls increased by 49.85% year-on-year, while the import volume decreased by 34.64% [12][10] Key Enterprises - The competitive landscape of the pearl farming industry features leading enterprises like Nanzhu Palace, Ruan's Pearls, and Oushiman, which leverage full industry chain layouts and core technology patents [17] - Ruan's Pearls, located in Zhejiang, focuses on freshwater pearl procurement, processing, and sales, while Hainan Hairun Pearl integrates pearl research, farming, and sales [19][20] Industry Trends 1. **Technological Innovation**: The industry is shifting from traditional methods to technology-driven approaches, with smart farming systems becoming mainstream [24] 2. **Diverse Consumption Scenarios**: The market is witnessing a trend where younger consumers drive demand for personalized and high-end pearl products [26] 3. **Accelerated Globalization**: Chinese pearl enterprises are transitioning from product export to brand and standard output, with a focus on global resource control and market integration [27]

Core Viewpoint - The research conducted by Professor Tong Xiaoling's team at Southwest University successfully achieved the sex reversal of silkworms from female to male using gene editing technology, marking a significant breakthrough in insect breeding and pest control strategies [1][2]. Group 1: Research Breakthrough - The study utilized CRISPR/Cas9 gene editing technology to target the key gene Bmdsx, which controls the sex determination in silkworms, leading to the forced skipping of specific exons that resulted in the development of male characteristics in previously female silkworms [2]. - The edited female silkworms exhibited male-specific traits, including an eight-segmented abdomen and male reproductive organs, capable of producing sperm similar to male silkworms [2]. Group 2: Implications for Industry - This breakthrough is expected to facilitate the breeding of higher yield and quality silkworm varieties, thereby promoting the development of the silk industry [2]. - The findings also have broader applications, as similar sex determination mechanisms were identified in various pests, including mosquitoes and cotton bollworms, providing a theoretical basis for developing new pest control strategies and ensuring sustainable agricultural production [2].

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]