来源：科技日报 科技日报记者 张佳欣 现代生命离不开三样东西：DNA、蛋白质和RNA。 但问题是，它们不可能同时出现。蛋白质就像建筑工人和建筑材料，没有蛋白质，DNA无法复制； DNA就像建筑蓝图，没有DNA，蛋白质无法构建。为了解开这个"先有鸡还是先有蛋"的难题，科学家 提出了一个影响深远的假说："RNA先行"。在这个设想中，RNA分子身兼双职：既是承载遗传信息的 蓝图，也是催化化学反应的"工人"。最早的生命，也许只是一些能自我复制的RNA分子。 这个假说听起来很完美，但几十年来始终卡在一个现实问题上：RNA这么复杂的分子，真的能在原始 地球那个混乱的环境里，自然、自发地形成吗？ 为了破解这个谜题，科学家不再孤立地测试单个化学反应，而是模拟一个更完整、更真实的早期地球环 境。 那个场景大约在43亿年前，地球由火山玄武岩构成了地下含水层。那时的大气中充满了二氧化碳、氮 气、水蒸气和来自火山喷发的硫化物，整个星球正经历着剧烈的地质变动。 科学家依据一个名为"不连续合成模型"（DSM）的路线图，将RNA的形成过程拆解为6个相互关联的化 学步骤，试图还原RNA"从零开始"生成的全过程：从大气中的简单气体出发，逐步生 ...

当前，随着创新药的热度从二级市场传导至一级市场，优质资产"争抢"现象凸显，叠加各种疗法的机遇 窗口加速更迭，如何预判下一阶段的赛道风口，成为全行业共同关注的核心议题。 红杉中国合伙人杨云霞在接受21世纪经济报道记者专访时指出，Biotech（生物科技）仍将是未来一段 时间的主流医疗投资方向，尤其值得重点关注的是"第二代技术范式的迭代"，例如从单靶单毒素向双靶 双毒素升级的ADC药物、从简单的双特异性抗体向更复杂的三特异性、多特异性抗体发展的抗体技 术、从自体CAR-T到通用型CAR-T再到体内CAR-T不断迭代的CAR-T疗法等等。 在杨云霞看来，上述技术范式其实都是创新药研发"分子形态"的结构进化和延伸，而在这些新的分子形 态中已上市的成熟产品数量仍相对有限，市场潜藏着大量未被满足的临床需求与未被挖掘的创新空间。 这既为医疗投资赛道提供了丰富的投资主题，也有望催生更多量级的BD案例。 技术迭代驱动创新进阶 麦肯锡有数据显示，截至今年9月，TOP20 MNC（跨国药企）也越来越多地从中国引进创新资产，中国 药企对外授权交易的占比已突破40%，其中1/2为双抗、ADC、RNA等"下一代疗法"。从转让方的角度 来 ...

Summary of Twist Bioscience Conference Call Company Overview - **Company**: Twist Bioscience (NasdaqGS:TWST) - **Industry**: Biotechnology, specifically focusing on DNA, RNA, and protein synthesis - **Key Customers**: Academic researchers, clinical diagnostic companies, biopharmaceutical companies, industrial chemical companies [1][2] Financial Performance - **Q4 Revenue**: $99 million - **Annual Revenue**: $376.6 million - **Guidance Exceeded**: Exceeded initial guidance by approximately $7 million despite a challenging economic environment [8][9] - **Gross Margin Improvement**: Increased by 20 percentage points over the last two years, now above 50% [9] - **Agility Beta Break-Even**: Projected to reach break-even by Q4 2026, with a loss of $8 million in the last quarter [9][10] Market Dynamics - **Stock Performance**: Despite strong quarterly updates, the stock is down over 40% year-to-date, indicating a disconnect between market perception and company performance [2][3] - **NGS Segment**: - Revenue of $208 million last year, accounting for about 55% of total sales, with over 20% year-over-year growth. - Guidance for fiscal 2026 implies about 12% growth [25][29] - Addressable market for MRD liquid biopsy estimated at $2.2 billion [25] - Overall NGS opportunity estimated at $3 billion with less than 10% market share [29] Customer Dynamics - **Key Customer Transition**: One significant NGS customer transitioning from clinical trials to commercial ramp, causing short-term revenue fluctuations [10][34] - **Volume Growth**: Excluding the impact of the key customer, the business is growing at approximately 20% [34][36] Strategic Insights - **R&D Focus**: Shifted from gross margin optimization to revenue growth, with flat operating expenses from 2022 to 2025 while growing revenue by 85% [16][17] - **Market Adaptability**: The company is positioned to pivot based on market dynamics, with a blended R&D approach across segments [20][23] - **Emerging Opportunities**: Identified new revenue streams from AI companies, with over $25 million in order growth anticipated from 2024 to 2025 [21][22] Pricing and Sales Strategy - **Pricing Dynamics**: Average Selling Price (ASP) decreased by 11% in Q4, attributed to increased volume in therapeutics and competitive pricing strategies [53][55] - **Pharma Orders**: Significant pharma orders in Q4 are expected to provide visibility and revenue growth in the first half of the fiscal year [56][57] Future Outlook - **Growth Potential**: The company aims to leverage its technology and market position to explore new revenue opportunities, with a focus on maintaining a competitive edge in both NGS and DNA synthesis segments [20][24] - **Long-term Vision**: Emphasis on adaptability and customer proximity to capitalize on emerging market trends and demands [23][24] Conclusion - Twist Bioscience demonstrates strong financial performance and growth potential despite market challenges. The company is strategically positioned to capitalize on emerging opportunities in the biotechnology sector while addressing short-term customer dynamics and pricing strategies.

Summary of Twist Bioscience Conference Call Company Overview - **Company**: Twist Bioscience (NasdaqGS:TWST) - **Industry**: Biotechnology, specifically focusing on DNA, RNA, and protein synthesis - **Key Customers**: Academic researchers, clinical diagnostic companies, biopharmaceutical companies, industrial chemical companies [1][2] Financial Performance - **Q4 Revenue**: $99 million - **Annual Revenue**: $376.6 million - **Guidance Exceeded**: Exceeded initial guidance by approximately $7 million despite a challenging economic environment [8][9] - **Gross Margin Improvement**: Increased by 20 percentage points over the last two years, now above 50% [9] - **Adjusted EBITDA**: Loss of $8 million in Q4, with a target to reach break-even by Q4 2026 [9][10] Market Dynamics - **Stock Performance**: Despite strong financial results, the stock is down over 40% year-to-date, indicating a disconnect between market perception and company performance [2][3] - **NGS Segment**: - Revenue of $208 million last year, accounting for about 55% of total sales, with over 20% year-over-year growth. - Guidance for fiscal 2026 implies about 12% growth [25][29] - Addressable market for MRD liquid biopsy estimated at $2.2 billion [25] - Overall NGS opportunity estimated at $3 billion with less than 10% market share [29] Customer Dynamics - **Key Customer Transition**: One significant NGS customer transitioning from clinical trials to commercial ramp, causing short-term revenue fluctuations [10][34] - **Growth Outside Diagnostics**: Strong performance in microarray conversion and new sequencer offerings [34][35] Strategic Insights - **R&D Focus**: Shifted from gross margin optimization to revenue growth, with a flat OPEX from 2022 to 2025 while growing revenue by 85% [16][17] - **Market Adaptability**: The company is positioned to pivot based on market dynamics, with a blended R&D approach across segments [20][23] - **Emerging Opportunities**: New revenue streams from AI-related services and antibody discovery, with significant order growth anticipated [21][22] Pricing and Volume Trends - **ASP Dynamics**: Average Selling Price (ASP) decreased by 11% in Q4, attributed to increased volume in therapeutics and competitive pricing strategies [53][55] - **Pharma Orders**: A record pharma order in Q4 is expected to provide visibility and revenue ramp in the first half of the year [56][57] Future Outlook - **Growth Projections**: The company aims for continued growth in both NGS and DNA synthesis/protein solutions, with potential for new revenue streams emerging from evolving market needs [19][20][22] - **Long-term Strategy**: Focus on maintaining high gross margins while pursuing aggressive growth strategies across various segments [18][24] Conclusion - Twist Bioscience is navigating a complex market landscape with strong financial performance and strategic adaptability. The company is poised for growth, leveraging its technological advantages and expanding into new market opportunities while addressing short-term challenges related to customer transitions and market perceptions.

Group 1 - The research team from University College London has successfully demonstrated the chemical connection between RNA and amino acids under enzyme-free conditions, providing new insights into the origin of life and protein synthesis [1][3][4] - The study integrates two major theories of life's origin: the "RNA world" and the "thioester world," suggesting that the origin of life may not have a single starting point but rather a collaborative evolution of metabolic and genetic systems [6][8] - The findings indicate that the chemical reaction necessary for RNA and amino acid connection likely occurred in early Earth's lakes or small pools rather than in the ocean, offering a more specific direction for scientists searching for the "cradle" of life [5][6] Group 2 - The research highlights the importance of understanding how RNA can connect with amino acids, which is crucial for grasping the mechanisms of life and protein synthesis [3][7] - The study's methodology involved using thioesters to activate amino acids, allowing for selective and spontaneous connections to RNA, which is vital for the stability and functionality of early life forms [4][6] - The implications of this research extend to potential applications in artificial life systems, in situ protein synthesis, and targeted drug delivery, emphasizing the relevance of understanding the chemical basis of life [7][8]

Core Insights - A breakthrough study by a research team from University College London has successfully demonstrated the chemical connection between RNA and amino acids under prebiotic conditions without enzymes, addressing a long-standing question in the origin of life research [4][5][6] Group 1: Research Findings - The study provides new insights into how proteins are synthesized, which is crucial for understanding the origin of life [5][6] - The research indicates that amino acids can spontaneously connect to RNA in early Earth environments, suggesting a possible pathway for the emergence of life [6][9] - The team utilized a milder method involving thioesters to activate amino acids, allowing for selective connections to RNA, which is essential for functional stability in early life forms [7][8] Group 2: Theoretical Implications - The findings merge the "RNA world" and "thioester world" theories, proposing that life may not have a single origin point but rather a collaborative evolution of metabolic and genetic systems [8][9] - This research narrows the gap between chemical evolution and biological evolution, providing a plausible chemical basis for the transition from non-living to living systems [9][10] Group 3: Future Directions - The research team aims to explore how RNA sequences preferentially bind to specific amino acids, which is vital for understanding the origins of genetic coding [10][11] - The implications of this study extend to potential applications in artificial life systems, in situ protein synthesis, and targeted drug delivery [10][11] - Continued exploration of the chemical microenvironment within cells may offer new strategies for disease prevention and treatment [10][11]

Core Insights - A breakthrough study by a research team from University College London successfully demonstrated the chemical connection between RNA and amino acids under enzyme-free conditions, addressing a long-standing question in the origin of life research [1][3][4] - The research integrates the "RNA world" and "thioester world" theories, suggesting that the origin of life may not have a single starting point but rather a collaborative evolution of metabolic and genetic systems through simple chemical reactions [6][8] Molecular Evolution - The study falls within the realm of molecular evolution, focusing on the self-assembly and functional evolution of biological macromolecules like RNA and proteins, as well as the formation of "primitive cells" [2][6] - The research highlights the importance of understanding how RNA connects with amino acids, which is crucial for comprehending the mechanisms of protein synthesis and the origin of life [3][4] Methodology and Findings - The research team utilized thioesters to activate amino acids, allowing them to connect with RNA in a controlled manner, which was previously unattainable with high-energy molecules that would decompose in water [4][5] - The findings suggest that these reactions likely occurred in early Earth's lakes or small pools rather than in the ocean, providing a more specific direction for scientists searching for the "cradle" of life [5][6] Implications for Future Research - The study opens avenues for further exploration into how RNA sequences preferentially bind to specific amino acids, which is essential for understanding the origin of the genetic code [7][8] - The research may also contribute to the development of artificial life systems, in situ protein synthesis, and targeted drug delivery, highlighting its potential applications in biotechnology and medicine [7][8] Broader Impact - The findings could bridge the gap between chemical evolution and biological evolution, offering a reasonable chemical basis for the transition from non-living chemical substances to living biological systems [6][8] - The research emphasizes the importance of the chemical microenvironment within cells, suggesting that imbalances may lead to molecular interactions abnormalities and metabolic disorders, which could inform new strategies for disease prevention [7][8]

Core Viewpoint - The article highlights the recent completion of nearly 100 million yuan in Pre-A round financing for Libo Bio, led by Tianshili Capital and Panlin Capital, showcasing the growing interest in biotech startups and the trend of venture capitalists seeking projects in research-intensive areas [2][9]. Group 1: Company Overview - Libo Bio was established in September 2022 by a team of three scientists, including Zhou Yaoqi, Zhan Jian, and Fang Chao, and initially received angel round financing from Sequoia China and Innovation Works [3][9]. - The company focuses on RNA research, leveraging AI to discover stable tertiary structures within RNA and predict their folding shapes and small molecule binding pockets [8][9]. - The founding team has extensive experience, with Zhou Yaoqi having nearly 30 years in structural computation, Zhan Jian being a core inventor of RNA stability methods, and Fang Chao specializing in small molecule drug development [6][9]. Group 2: Investment and Financing - The recent Pre-A round financing of nearly 100 million yuan was supported by Tianshili Capital and Panlin Capital, with follow-on investments from Yuan Sheng Venture Capital and other funds [2][9]. - The financing is seen as a significant step in transforming cutting-edge research into new productive forces, as emphasized by Yan Ning, the director of Shenzhen Bay Laboratory [5][6]. Group 3: Industry Trends - The article reflects a broader trend in the venture capital landscape, where investors are increasingly targeting projects in research-heavy environments, particularly those associated with prestigious research institutions [4][9]. - The success of Libo Bio exemplifies the effective transition from laboratory research to clinical applications, aligning with Shenzhen's efforts to promote the commercialization of frontier research [5][6].

Core Insights - The research team at Harbin Institute of Technology has successfully constructed a de novo nucleotide synthesis metabolic pathway within artificial cells, laying the foundation for autonomous artificial cell development [1][2] - Nucleotides are essential components for RNA synthesis, and the ability to synthesize them in situ is crucial for the autonomy and long-term stability of artificial cells [1] Group 1 - The metabolic pathway starts with ammonium bicarbonate to synthesize uridine triphosphate (UTP) and involves eight enzymes, including CPS, ATC, DHO, DHODH, RPPK, UMPs, UK, and NDK [2] - An ATP regeneration system composed of creatine kinase (CK) and phosphocreatine was introduced to drive the metabolic pathway [2] - Under optimized conditions, the pathway can produce 0.85 millimoles per liter of UTP within three hours, enabling RNA transcription in artificial cells [2]