Workflow
基因治疗
icon
Search documents
被嫌弃的AAV病毒递送系统
3 6 Ke· 2025-10-09 23:18
安全性问题频出,Sarepta的AAV基因疗法Elevidys因患者死亡事件被FDA勒令暂停销售,Capsida Biotherapeutics公司的AAV相关临床试验也因儿童患者死 亡被迫中止。 加之"天价"问题,商业化局面迟迟难以打开,近一年来,AAV基因治疗领域退潮信号愈发强烈:今年2月,辉瑞宣布终止最后一个AAV项目Beqvez;5月, 福泰制药明确表示不再将AAV用作基因治疗项目的递送机制;9月底,渤健更是宣布直接清空了全部AAV管线。 昔日炙手可热的AAV赛道,突然间弥漫着撤退、危险的气息,这与几年前的盛况形成了鲜明对比。 作为曾经的明星载体,AAV成功助推了一批划时代的基因疗法问世,也吸引着无数biotech与大药企的押注。 然而,随着临床深入与商业落地加速,AAV的隐患无处遁形:高剂量毒性、免疫应答失控、天价成本……AAV载体一步步滑落神坛,甚至被大药企纷 纷"嫌弃"、抛弃。 困境,远比想象中更残酷。从被争相追逐的"黄金工具",到被质疑甚至放弃的递送系统,AAV载体未来何去何从? 三大硬伤 基因治疗草莽初创之际,其他递送系统尚存在诸多不成熟因素,AAV以其特性——结构稳定、表达持久、较低的免疫 ...
Nature Biotechnology:周昌阳/孙怡迪/谢峻团队开发新型表观编辑器,单次给药即可高效、长效降血脂
生物世界· 2025-10-01 10:50
编辑丨王多鱼 排版丨水成文 基因编辑技术,如CRISPR/Cas9和新一代的碱基编辑技术,通过永久性地改变DNA序列来修正致病基因, 是功能强大的治疗工具。这些前沿技术在修正基因时,或依赖于DNA断裂后的细胞修复,或直接对单个 DNA碱基进行转换。尽管这些技术的精准性在不断迭代提升,但如何确保在复杂的人体环境中完全避免任 何非预期的、永久性的序列改变,仍是该领域在迈向更广泛临床应用时需要持续关注和完善的重要方向。 正是在这一背景下,一种旨在补充现有技术、为基因治疗提供更多选择的策略——表观遗传编辑,获得了 越来越多的关注。它如同基因表达的"调控开关",无需改动DNA序列,而是通过在特定的基因组位点添加 或移除表观遗传化学修饰,来精准地调控目标基因的"开启"或"关闭"。这种只改变基因修饰而不改变基因 序列的方式,为基因治疗的安全性提供了新的思路。 近期,锌指蛋白和dCas9的表观遗传编辑疗法已经展现出了巨大潜力,已有研究在小鼠和非人灵长类体内 成功抑制了PCSK9的表达,从而有效降低了血液中的胆固醇水平。 PCSK9是调控血液中"坏胆固醇" (LDL-C) 的关键蛋白,抑制它已成为预防和治疗心血管疾病的重要策略 ...
Lexeo Therapeutics (NasdaqGM:LXEO) Conference Transcript
2025-09-30 18:02
Lexeo Therapeutics Conference Call Summary Company Overview - **Company**: Lexeo Therapeutics (NasdaqGM:LXEO) - **Industry**: Clinical stage genetic medicines - **Focus**: Treatment of rare diseases with high unmet medical needs, specifically Friedreich's ataxia and arrhythmogenic cardiomyopathy [2][3] Key Programs 1. **Friedreich's Ataxia (FA)** - **Therapy**: Gene therapy using the ABRH10 vector to deliver the frataxin gene to the heart and skeletal muscle - **Current Status**: Rapidly moving into a pivotal study in 2026 - **Clinical Data**: Achieved a 23% reduction in left ventricular mass index (LVMI) in patients with elevated LVMI, exceeding the FDA's required 10% reduction [9][10] - **FDA Engagement**: Alignment on co-primary endpoints of LVMI reduction and frataxin expression, with 100% of patients showing frataxin expression post-treatment [10][11] 2. **Arrhythmogenic Cardiomyopathy (PKP2)** - **Focus**: Targeting the PKP2 mutation, the most common genetic cause of arrhythmogenic cardiomyopathy - **Current Status**: Eight patients dosed, with a phase one study readout expected by the end of 2025 [3][30] - **Patient Experience**: Patients experience significant anxiety and fear due to symptoms like skipped heartbeats and potential shocks from defibrillators [30][31] Clinical Data and Endpoints - **Friedreich's Ataxia**: - Significant changes in LV mass observed, with a focus on achieving statistical power in the pivotal trial [8][9] - Safety profile is strong, with no significant elevations in liver enzymes or adverse events reported [24][25] - **Arrhythmogenic Cardiomyopathy**: - Focus on multiple clinical endpoints including premature ventricular contractions (PVCs) and right ventricular function [34][36] - Aim to demonstrate improvement across multiple domains to show therapeutic benefit [39] Safety and Regulatory Considerations - **Safety Profile**: Lexeo emphasizes a compelling safety profile due to lower dosing compared to other gene therapies, with no drug-related serious adverse events reported [25][41] - **Regulatory Engagement**: Ongoing discussions with the FDA to finalize the size of the pivotal study, expected to be a 2026 event [11][45] Market Potential and Commercial Strategy - **Target Market**: Initial focus on high LVMI patients, with potential expansion to earlier-stage patients as treatment evolves [26][27] - **Cash Runway**: Recently completed a capital raise, providing a runway into 2028, well-positioned for upcoming milestones [47] Conclusion - Lexeo Therapeutics is advancing its gene therapy programs with a strong focus on safety and efficacy, aiming to address significant unmet needs in rare cardiovascular diseases. The company is well-capitalized and strategically positioned for future clinical trials and market entry.
基因疗法成功延缓亨廷顿病发展
Ke Ji Ri Bao· 2025-09-30 01:17
Group 1 - The core finding of the study indicates that the gene therapy AMT-130 has successfully slowed disease progression in early-stage Huntington's disease patients by approximately 75% over three years compared to the control group, marking a significant advancement in treatment options [1][2] - AMT-130 utilizes a harmless virus to deliver a microRNA sequence to the affected areas of the brain, effectively "turning off" the defective gene responsible for abnormal protein production [1] - The therapy targets the two brain regions most affected by Huntington's disease, requiring precise injection guided by real-time brain scans, with the entire procedure taking 12 to 18 hours [1] Group 2 - The company plans to submit an application to the U.S. Food and Drug Administration (FDA) early next year, with the potential for the drug to be available on the market by 2027 if approved [3] - Initial results show that the therapy is generally safe, with common side effects including headaches and confusion, which are mostly self-resolving or manageable with steroids [2]
自带导航,主动敲门,CRISPR有了新型“快递车”
Ke Ji Ri Bao· 2025-09-23 08:52
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]
Cell系列综述:舒易来团队等系统总结耳聋治疗的范式转变——临床基因治疗恢复听力
生物世界· 2025-09-23 08:30
编辑丨王多鱼 排版丨水成文 近日, 复旦大学附属眼耳鼻喉科医院耳鼻喉科、耳鼻喉科研究院 舒易来 、 李华伟 , 哈佛医学院耳鼻咽喉头颈外科 陈正一 和 加州大学欧文分校听力研究中心 曾凡钢 合作 (共同一作为 复旦大学附属眼耳鼻喉科医院耳鼻喉科、耳鼻喉科研究院 的 韩双 、 陈紫婷 和 王大奇 ) 在 Cell Press 旗下综述期刊 Trends In Molecular Medicine 上发表了题为: Clinical gene therapy restores hearing: a paradigm shift 的综述论文 。 亮点 以腺相关病毒 (AAV) 为载体的基因治疗策略,在动物模型中已被证实对20多种基因突变引起的遗传性耳聋有效。 2022 年,复旦大学附属眼耳鼻喉科医院率先完成临床试验注册,并在中国上海成功实施了 全球首例遗传性耳聋基因治疗 ,成为先天性耳聋领域首次基因治疗临 床实践。2023-2025 年期间,全球另有 7 项针对 OTOF 基因突变所致遗传性耳聋的基因治疗临床试验在 8 个国家注册。截止目前,5 项临床试验已报道通过双 AAV 递送策略成功恢复受试者听力,为遗传性耳聋 ...
CRISPR有了新型“快递车”
Ke Ji Ri Bao· 2025-09-23 01:36
Core Insights - CRISPR technology represents a revolutionary gene-editing tool that offers unprecedented hope for treating genetic diseases, 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 "gene delivery vehicle" that enhances the efficiency of delivering CRISPR tools into cells while reducing damage and improving gene repair accuracy [3] Delivery Mechanisms - Current methods for delivering CRISPR into cells primarily rely on two vehicles: modified viruses and lipid nanoparticles (LNPs). Viruses are efficient but pose safety risks due to immune responses, while LNPs are safer but have lower delivery efficiency [4][5] - 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 [6] Performance Metrics - The new delivery vehicle demonstrates over three times the efficiency of traditional lipid nanoparticles, with significantly lower toxicity to cells. The success rate of gene editing has also increased by over 60% [6] - This technology is modular, allowing for targeted delivery to specific cell types, such as liver, brain, or cancer cells, by altering the DNA shell's "code" [7] Clinical Applications - Seven drugs based on similar spherical nucleic acid technology are currently in human clinical trials, with some testing cancer treatment efficacy. The new technology is being promoted by several biotech companies for rapid clinical trial application [7] - The breakthrough emphasizes that while CRISPR itself is powerful, the method of delivery is equally critical, marking a significant advancement in gene therapy capabilities [7]
自带导航 主动敲门 CRISPR有了新型“快递车”
Ke Ji Ri Bao· 2025-09-22 23:36
Core Viewpoint - CRISPR technology has made significant advancements in gene editing, but the challenge remains in effectively delivering these tools to the target cells safely and efficiently. A breakthrough from Northwestern University has introduced a new delivery system that enhances the efficiency and accuracy of CRISPR applications in gene therapy [1][3]. Group 1: Current Delivery Methods - Current methods for delivering CRISPR include modified viruses and lipid nanoparticles (LNPs), each with their own limitations. Viruses are efficient but can trigger immune responses, while LNPs are safer but have low delivery efficiency [2]. - Another method involves ex vivo editing, which is complex and costly, making it impractical for most diseases. Thus, there is a need for a safer and more efficient in vivo delivery system [2]. Group 2: New Delivery System - The new system, termed "Lipid Nanoparticle Spherical Nucleic Acids" (LNP-SNA), features a DNA shell that enhances visibility and uptake by cells, significantly improving delivery efficiency [3]. - This innovative delivery vehicle has shown to be over three times more efficient in entering cells compared to traditional lipid nanoparticles, with a significantly lower toxicity profile. The success rate of precise gene editing has increased by over 60% [3]. Group 3: Versatility and Future Applications - The LNP-SNA system is modular, allowing for customization to target specific cell types, such as liver, brain, or cancer cells, thereby enabling precise delivery [4]. - Seven drugs based on similar spherical nucleic acid technology are currently in human clinical trials, with some focusing on cancer treatment. The technology is being promoted by various biotech companies for rapid clinical application [4].
张江独角兽,完成超6亿元融资 | 融资周报(2025年第34期)
Sou Hu Cai Jing· 2025-09-17 06:11
Financing Overview - A total of 23 financing events occurred in Shanghai this week, with Zhangjiang accounting for 7 and Lingang for 2 [2] - The financing amount disclosed this week reached approximately 1.731 billion yuan, with 6 out of 23 events revealing their amounts [4] - The number of financing events increased by 5 compared to the previous week, which had 18 events [4] Company Dynamics - YaoTang Biotech announced research results on LNP-mRNA mediated in vivo gene editing of hematopoietic stem cells on August 12 [3] - On September 4, RuShen Robotics was selected for Tencent's 2025 Silver Technology Partner Program [3] - HengRui Medicine's subsidiary received approval for its first mRNA gene drug Phase II clinical trial on September 10 [5] - The China-Russia Medical Technology and Equipment Cooperation Center was established in Pudong on September 11 [5] - AstraZeneca's long-acting C5 complement inhibitor was launched in China on September 12 [5] Financing Rounds - The majority of financing events this week were in the angel round, totaling 9, followed by 7 in the A round [6] - B round financing reached a significant amount of 60 million USD [6] Industry Focus - Financing events this week spanned 11 industries, with the healthcare sector leading with 5 events, followed by artificial intelligence with 3 [9] Notable Financing Highlights - Zhenqu Technology completed over 600 million yuan in E round financing on September 8, led by Guotou Innovation and Guotou Investment [13] - Yijielike completed 60 million USD in B round financing on September 8, led by Longpan Investment [15] - New Electric Hero secured nearly 300 million yuan in strategic financing on September 10, exclusively invested by BAI Capital [17] - YaoTang Biotech completed over 300 million yuan in B round financing on September 10, led by AstraZeneca's CICC Medical Industry Fund [19] - RuShen Robotics completed several million yuan in angel+ round financing on September 9, exclusively funded by Daotong Investment [22] Hot Industry Focus - This week saw 5 financing events related to healthcare, including 2 in gene technology: Yijielike's 60 million USD B round and YaoTang Biotech's over 300 million yuan B round [24] - The surge in gene therapy investments is driven by policy support, with Shanghai's Science and Technology Commission announcing a special fund for gene therapy research, with a maximum grant of 5 million yuan per project [24]
传奇科学家乔治·丘奇的抗衰老论文被撤稿!论文作者曾亲自“当小白鼠”,宣称年轻20岁
生物世界· 2025-09-07 04:03
Core Viewpoint - The article discusses a research paper published by a team from Rutgers University, BioViva, and Harvard University, which proposed a gene therapy using cytomegalovirus (CMV) to extend healthy lifespan in mice. The paper was later retracted due to data discrepancies identified during an internal review [5][8][12]. Research Findings - The study demonstrated that gene therapies targeting TERT and FST genes could extend the lifespan of mice by approximately 40% without increasing cancer risk [5][12]. - Mice treated with TERT gene therapy had a median lifespan of 37.5 months, while those treated with FST gene therapy had a median lifespan of 35.1 months, compared to 26.7 months for the control group [12][13]. - The therapies also improved metabolic functions, glucose tolerance, and prevented weight loss and hair loss, indicating a broader impact on health beyond lifespan extension [13]. Gene Therapy Mechanism - TERT gene therapy activates telomerase, which can extend telomeres and potentially reverse aging processes, while FST gene therapy enhances muscle mass and function [10][11]. - CMV was chosen as a delivery vector due to its ability to carry larger genetic payloads and its safety profile, as most humans are already infected with it without symptoms [11]. Retraction Reasons - The paper was retracted following the discovery of issues in the data presented in figures, including over-saturation and image duplication [15][16]. - The retraction was supported by George Church, one of the authors, who acknowledged the lack of sufficient data backup but maintained that the core findings were not fundamentally flawed [20]. Author Responses - Elizabeth Parrish expressed shock at the retraction, arguing that the image issues were non-substantial and had been previously corrected [21]. - Zhuo Hua, another co-author, indicated a lack of necessity to respond due to retirement [21]. - The first author, Dabbu Kumar Jaijyan, stated there was nothing to address regarding the retraction [22].