更新于：2024-11-01

SOX2

更新于：2024-11-01

基本信息

别名

SOX2、SRY-box transcription factor 2、Transcription factor SOX-2

简介

Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Binds to the proximal enhancer region of NANOG (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency (PubMed:18035408). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity). May function as a switch in neuronal development (By similarity).

关联

项与 SOX2 相关的药物

STEMVAC(EpiThany)

靶点

CDH3 x ENG x MDM2 x SOX2 x Yb-1

作用机制

CDH3抑制剂 [+4]

在研机构

EpiThany, Inc.

原研机构

EpiThany, Inc.

在研适应症

乳腺癌

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

ER-100

靶点

KLF4 x POU5F1 x SOX2

作用机制

KLF4 modulators [+2]

在研机构

Life Biosciences, Inc.初创企业

原研机构

Life Biosciences, Inc.初创企业

在研适应症

青光眼

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

EPD-301

靶点

SOX2

作用机制

SOX2抑制剂

在研机构

Takeda Pharmaceutical Co., Ltd. [+2]

原研机构

EPD Biotherapeutics, Inc.

在研适应症

鳞状细胞肺癌 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 SOX2 相关的临床试验

NCT05242965 / Recruiting临床2期IIT

A Phase II Randomized Study of Safety and Efficacy of a Multiple Antigen Vaccine (STEMVAC) in Non-Small-Cell Lung Cancer Patients

This phase II trial tests whether CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine (STEMVAC) works to shrink tumors in patients with stage IV non-small cell lung cancer. STEMVAC targets specific immunogenic proteins that help lung cancer cells to grow. STEMVAC is made up of deoxyribonucleic acid (DNA), which is a natural substance in every living organism. DNA acts like a blueprint that tells all the cells in your body how to function. The DNA used in this study contains instructions for your body to produce parts of the 5 proteins the investigators identified (CDH3, CD105, YB-1, MDM2 and SOX2). STEMVAC is given with granulocyte-macrophage colony stimulating factor (GM-CSF) which is being used as an adjuvant to help create a stronger immune response. Giving STEMVAC with GM-CSF to patients while on maintenance therapy for non-small cell lung cancer (NSCLC) may help activate certain immune cells to recognize and kill lung cancer cells.

开始日期2023-03-24

申办/合作机构

University of Washington

[+1]

NCT05455658 / Recruiting临床2期IIT

A Phase II Trial of The Immunogenicity of a DNA Plasmid Based Vaccine (STEMVAC) Encoding Th1 Selective Epitopes From Five Antigens Associated With Breast Cancer Stem Cells (MDM2, YB1, SOX2, CDC25B, CD105) in Participants With Early Stage Triple Negative Breast Cancer

This phase II trial studies the effect of DNA plasmid based vaccine (STEMVAC) in treating patients with patients with stage IB-III triple negative breast cancer. STEMVAC may wake up the immune system in patients who have had a diagnosis of triple negative breast cancer and have been treated. STEMVAC targets proteins that are expressed on breast cancer cells and works by boosting the immune system to recognize and destroy the invader cancer cell proteins that are causing the disease. The purpose of this trial is to test the immune system's response to STEMVAC.

开始日期2022-11-17

申办/合作机构

University of Washington

[+2]

NCT02157051 / Active, not recruiting临床1期IIT

A Phase I Trial of the Safety and Immunogenicity of a Multiple Antigen Vaccine (STEMVAC) in HER2 Negative Advanced Stage Breast Cancer Patients

This phase I trial studies the side effects and best dose of multiantigen deoxyribonucleic acid (DNA) plasmid-based vaccine in treating patients with human epidermal growth factor receptor 2 (HER2)-negative stage III-IV breast cancer. Multiantigen DNA plasmid-based vaccine may target immunogenic proteins expressed in breast cancer stem cells which are the component of breast cancer that is resistant to chemotherapy and has the ability to spread. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells.

开始日期2015-06-01

申办/合作机构

University of Washington

[+2]

100 项与 SOX2 相关的临床结果

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100 项与 SOX2 相关的转化医学

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0 项与 SOX2 相关的专利（医药）

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10,583

项与 SOX2 相关的文献（医药）

2025-03-01·Neural Regeneration Research

Postnatal development of rat retina: a continuous observation and comparison between the organotypic retinal explant model and in vivo development

Article

作者: Chen, Xinlin ; Zhang, Zhichao ; Wang, Xiou ; Luan, Yan ; Kang, Qianyan ; Wang, Rui ; Zhang, Hanyue ; Ma, Bo ; Wang, Xin ; Zhou, Sijia ; Hu, Baoqi

JOURNAL/nrgr/04.03/01300535-202503000-00033/figure1/v/2024-06-17T092413Z/r/image-tiff The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures. However, the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies. Thus, we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina. In this study, we showed that postnatal retinal explants undergo normal development, and exhibit a consistent structure and timeline with retinas in vivo. Initially, we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells. We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin, respectively. Ki-67- and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis, and exhibited a high degree of similarity in abundance and distribution between groups. Additionally, we used Ceh-10 homeodomain-containing homolog, glutamate-ammonia ligase (glutamine synthetase), neuronal nuclei, and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells, Müller glia, mature neurons, and microglia, respectively. The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas. Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development. The findings confirm the accuracy and credibility of this model and support its use for long-term, systematic, and continuous observation.

2025-01-01·Gene

Bmal1 regulates the stemness and tumorigenesis of gliomas with the Wnt/β-catenin signaling pathway

Article

作者: Han, Qian ; Su, Dongpo ; Li, Mei ; Xia, Hechun ; Fan, Heng

BACKGROUNDThe circadian rhythm gene Brain and Muscle Arnt-like1 (Bmal1) acts as a transcription factor and plays a crucial role in oncogenesis and embryonic development. Bmal1 is notably overexpressed in various tumors, including glioma. However, the precise mechanisms underlying the elevated Bmal1 expression in glioma malignancy remain unclear.METHODSThis study employed multiple databases, including The Cancer Genome Atlas (TCGA), GTEx, and cBioportal, to analyze Bmal1 mRNA expression in gliomas, evaluate its prognostic significance, investigate transcriptome alterations, identify key signaling pathways associated with Bmal1, and examine its interaction with tumor stem cells. Additionally, experimental validation was performed to confirm Bmal1's regulatory effects on glioma stem cells.RESULTSOur analysis revealed differential Bmal1 expression across glioma grades and molecular subtypes. Moreover, Bmal1 significantly influences several tumor-related signaling pathways, notably the Mapk, Met, and Wnt pathways, and is actively involved with stem cells. A strong positive correlation was observed between Bmal1 and glioma stem cell markers, such as Nestin, Sox2, and Cd133. Experimental validation confirmed that Bmal1 promotes stem cell expansion and tumor progression via the Wnt/β-catenin pathway.CONCLUSIONThis study underscores the critical regulatory function of Bmal1 in glioma development. The interaction between Bmal1 and glioma stem cells appears to significantly impact glioma initiation and progression.

2025-01-01·Food Chemistry

Dietary nucleotides drive changes in infant fecal microbiota in vitro and gut microbiota-gut-brain development in neonatal rats: A potential “nitrogen source” for early microbiota growth

Article

作者: Lin, Guopeng ; Qu, Zhihao ; Wang, Gang ; Chen, Wei ; Zhang, Bo ; Wang, Linlin ; Tian, Peijun ; Zhang, Heng ; Guo, Min

Various dietary factors in human milk are important nutrients for the formation of the infant gut microbiota (GM). While promoting the growth of the GM, some human milk components that are difficult to absorb and utilize will be broken down by the GM, and converted into nutrients that the baby can use, such as breast milk oligosaccharides-the 'carbon source' for infant GM. This study reveals that nucleotides (NTs), significant non-protein nitrogen sources in human milk, can enhance the abundance of beneficial microbial genera such as g_Bifidobacterium, g_Bacteroides, and g_Blautia in in vitro fecal fermentation fluids of infants at low doses (2 mg/mL). Conversely, high doses of NTs (20 mg/mL) increased the abundance of g_Escherichia-Shigella. Furthermore, low-dose NTs fermentation broth significantly enhanced the expression of neurodevelopmental marker genes such as Tuj1, Sox2, Dcx, and NeuN in NE-4C neural stem cells, whereas a single NTs digestion broth did not exhibit significant activity. However, in vivo studies using neonatal rats as a model demonstrated that both low-dose NTs fermentation broth and NTs digestive juices promoted behavioral development in neonatal rats (PND 20) and neuron maturation in the prefrontal cortex and hippocampus. Non-targeted metabolomics results indicate that low-dose dietary NTs promote the production of certain neuroregulatory metabolites in infant fecal fermentation, such as uridine, L-tyrosine, L-glutamic acid, and succinic acid. These findings suggest that NTs may serve as an important "nitrogen source" during GM formation in early life and have a dose effect in driving the development of the microbiota-gut-brain axis in early life.

项与 SOX2 相关的新闻（医药）

2024-10-31

·生物探索

Mol Cell | HOXDeRNA 通过与基因组广泛结合激活癌症转录程序和超级增强子

引言胶质瘤是中枢神经系统中最常见的恶性肿瘤，预后极差，其转化机制涉及多种基因突变。PRC2是一个组蛋白甲基化酶复合物，其催化亚基EZH2在肿瘤抑制基因的沉默中起关键作用。PRC2通过在组蛋白H3的第27个赖氨酸上添加甲基标记（H3K27Me3）来沉默基因【1】。EZH2可以与多种RNA结合，包括富含鸟嘌呤的序列和RNA四重氢键 (rG4)【2】。尽管 EZH2-RNA结合的选择性存在争议，但一些lncRNA的功能与其PRC2结合能力相关。HOXDeRNA是一种增强子相关的lncRNA，在正常脑组织中沉默，但在胶质瘤中普遍激活【3】。高水平的HOXDeRNA与胶质瘤进展和GBM患者生存期缩短相关。之前的研究表明，在胶质瘤细胞中靶向激活HOXDeRNA会促进其转化为胶质瘤样细胞。但是，HOXDeRNA是如何通过其RNA四重氢键结构与EZH2相互作用，从而在整体范围内激活癌症转录程序和超级增强子的，目前尚不清楚。近日，来自美国波士顿布莱根妇女医院哈佛医学院神经病学系的Anna M. Krichevsky研究团队在在Molecular Cell杂志上发表题为HOXDeRNA activates a cancerous transcription program and super enhancers via genome-wide binding的研究论文，该研究发现了lncRNA HOXDeRNA通过与EZH2结合并消除其抑制作用，在胶质瘤中激活了广泛的癌症转录程序和超级增强子，从而将星形胶质细胞转化为类似于胶质瘤干细胞的细胞。研究人员通过CRISPR系统激活HOXDeRNA后，观察到星形胶质细胞从贴壁生长转变为形成球形，形态发生显著变化。转录组分析揭示了HOXDeRNA激活后，大量基因表达发生改变，包括细胞粘附、生长因子和酪氨酸激酶相关基因，以及35个关键的胶质瘤转录因子(TFs)。这些TFs不仅包括SOX2和OLIG2等干细胞相关TFs，还包括EGFR、PDGFRA、BRAF和TERT 等已知的癌症驱动基因。这些基因的激活定义了转化后星形胶质细胞的转录组和胶质瘤样身份，表明HOXDeRNA在驱动星形胶质细胞向胶质瘤转化中发挥重要作用。研究人员利用ChIRP-seq和iMARGI技术揭示了HOXDeRNA在星形胶质细胞和胶质瘤干细胞中与基因组广泛的结合，主要位于基因启动子和外显子区域。HOXDeRNA结合的基因在正常脑组织和胶质瘤细胞中通常被PRC2标记沉默，但在转化后失去PRC2标记并表达上调。这表明HOXDeRNA通过与PRC2结合并去除其抑制作用来激活这些基因，从而在胶质瘤发生发展中发挥关键作用。 iMARGI和ChIRP-seq分析发现，HOXDeRNA主要与表达上调的基因的CpG岛结合，而CpG 岛通常位于基因启动子区域。这些超级增强子（super enhancers，SEs）与SOX2和OLIG2等TFs的结合位点高度富集，表明这些TFs可能调节这些SEs。通过敲低SOX2和OLIG2，可以显著降低胶质瘤SEs的活性，并减少球形形成，表明这些TFs对SEs的激活和星形胶质细胞的转化至关重要。此外，SOX2和OLIG2敲低还导致SEs相关基因表达下调，表明SEs激活可能介导了HOXDeRNA对基因表达的影响。研究人员通过CLIP实验发现EZH2与未剪接的HOXDeRNA结合，而不是成熟型HOXDeRNA。通过CRISPR基因编辑，敲除HOXDeRNA中的rG4结构会降低其与EZH2的结合并减少PRC2 标记的基因的激活。这些结果表明，EZH2可能招募核内的HOXDeRNA到染色质上，而rG4 结构介导了这种结合。此外，敲除 rG4-1 结构会降低星形胶质细胞的转化能力，表明rG4-1 结构在HOXDeRNA的转化功能中发挥重要作用。图1 HOXDeRNA 通过与基因组广泛结合激活癌症转录程序和超级增强子（Credit: Molecular Cell）总之，该研究揭示了长链非编码RNA HOXDeRNA在胶质瘤发生发展中的关键作用机制。发现了HOXDeRNA通过rG4结构结合EZH2并招募到PRC2标记的基因组区域，从而去除PRC2对关键胶质瘤转录因子和超级增强子的抑制，最终激活多个癌症驱动基因，驱动星形胶质细胞向胶质瘤转化。这项研究为胶质瘤的发病机制提供了新的见解，并为开发新的治疗策略提供了潜在的靶点。参考文献 1. Cao, R., and Zhang, Y. (2004). The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr. Opin. Genet. Dev. 14, 155-164. 2. Wang, X., Goodrich, K.J., Gooding, A.R., Naeem, H., Archer, S., Paucek, R.D., Youmans, D.T., Cech, T.R., and Davidovich, C. (2017). Targeting of polycomb repressive complex 2 to RNA by short repeats of consecutive guanines. Mol. Cell 65, 1056-1067.e5. 3. Deforzh, E., Uhlmann, E.J., Das, E., Galitsyna, A., Arora, R., Saravanan, H., Rabinovsky, R., Wirawan, A.D., Teplyuk, N.M., El Fatimy, R., et al. (2022). Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus, and neoplastic transformation in glioma. Mol. Cell 82, 1894–1908.e5. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.molcel.2024.09.018 责编|探索君排版|探索君来源|BioArt End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

基因疗法临床结果

2024-10-21

·GlobeNewswire-Health Care

Life Biosciences Presents at AAO Highlighting Progress of Nonhuman Primate Studies Evaluating Partial Epigenetic Reprogramming to Restore Visual Function

Data replicate and expand upon the potential of ER-100 to improve retinal ganglion cell function and restore visual function in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy (NAION)BOSTON, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Life Biosciences (“Life Bio”), a biotechnology company advancing innovative cellular rejuvenation technologies to reverse diseases of aging and injury and ultimately restore health for patients, today announced new data presented at the 2024 American Association of Ophthalmology (AAO) Annual Meeting that took place in Chicago, Illinois from October 18-21, 2024. Results replicate previously reported nonhuman primate (NHP) data and further expand our knowledge on dosing and timing of treatment. ER-100, a novel partial epigenetic reprogramming gene therapy containing Oct-4, Sox-2 and Klf-4 (OSK), was administered via a single intravitreal injection along with daily systemic doxycycline to NHPs with a NAION-like injury. Immunohistochemistry confirmed expression of each transcription factor (Oct-4, Sox-2 and Klf-4) in discrete cells in the perifoveal regions in ER-100 treated NHPs relative to vehicle. Furthermore, ER-100 significantly reduced deficits in pattern electroretinogram and axon density measures when administered in both prevention and rescue paradigms. Collectively, these results demonstrate that ER-100 successfully targets retinal ganglion cells and reduces the loss of visual function in an NHP model of NAION. Life Bio remains on track to initiate the first human clinical study evaluating ER-100 for optic neuropathies in the second half of 2025. “Partial epigenetic reprogramming has the potential to restore visual function for those with optic neuropathies such as NAION and glaucoma,” said Sharon Rosenzweig-Lipson, Ph.D., Chief Scientific Officer of Life Bio. “The data shared today replicate and build upon our understanding of the dosing of ER-100 and the timing of the treatment window relative to the onset of NAION-related damage. We look forward to advancing this program toward human clinical trials next year for patients affected by these age-related optic neuropathies.” About Life Biosciences Life Biosciences is a biotechnology company advancing innovative cellular rejuvenation platforms to reverse diseases of aging and injury and ultimately restore health for patients. The company is focusing on two platforms targeting key mechanisms underlying aging biology, epigenetic reprogramming and chaperone-mediated autophagy, to restore cells to a more youthful state. Therapies developed within these platforms have the potential to prevent, treat, and/or reverse multiple aging-related diseases. For more information, please visit www.lifebiosciences.com or follow us on Twitter and LinkedIn. Media Contact Kristin Politi, Ph.D.LifeSci Communicationskpoliti@lifescicomms.com(646) 876-4783

细胞疗法基因疗法

2024-10-15

·动脉网

用细胞重编程技术对抗衰老、核心管线即将推进临床，这家企业的抗衰疗法获FDA肯定

2023年10月25日，在FDA生物制品评价与研究中心（CBER）的产品监管建议（INTERACT）会议上，抗衰企业Turn Biotechnologies（以下简称“Turn Bio”）基于mRNA的细胞再生疗法TRN-001获得了FDA的积极反馈。会议上，Turn Bio与FDA重点讨论了TRN-001的未来发展方向。结果表示，TRN-001有望成为首个在细胞水平上修复受损皮肤、改善皮肤完整性并减少炎症和细胞衰老的治疗方法。此次会议的结果表明，Turn Bio有望成为首家将基于mRNA的细胞再生疗法推向临床试验的公司。作为抗衰领域的明星企业，Turn Bio成立于2019年，现总部位于硅谷。公司专注于通过表观遗传重编程技术研发mRNA药物，进而从细胞层面修复组织从而使细胞恢复年轻活力，修复衰老过程造成的损害。基于专有的mRNA技术平台ERA™和药物传递平台eTurna™，Turn Bio目前开发了多个候选管线，治疗领域包括皮肤科、骨关节炎和软骨损伤、免疫学、眼科、肌肉组织损伤等。其中，TRN-001进展较快，目前处于临床前研究阶段，即将推向临床试验阶段。核心技术平台ERA™：可高效逆转细胞老化并维持细胞特性将成熟细胞重编程转化为干细胞的过程被称为“重编程”。2006年，日本科学家山中伸弥发现4种转录因子（Oct3/4、Sox2、Klf4、c-Myc）可以将高度分化的体细胞逆转为多能干细胞，使其重新具备分化成不同类型细胞的能力，这个过程被称为重编程。重编程技术会产生“去分化”和“年轻化”两种影响，即能够将细胞中与衰老相关的表观遗传信息重编程，使细胞转变为类似于胚胎干细胞的状态，从而将细胞的表观遗传时钟调拨回零，实现细胞水平层面的“返老还童”。而使细胞发生重编程主要通过两种形式实现，分别是：一、通过递送外源的转录因子系统进入到细胞或动物中；二、激活或调控内源的命运转录因子表达。其中，从第一种形式看，可以通过将细胞命运转录因子包装进病毒或mRNA，而后将其注入细胞或动物中，以传递想要实现的功能。基于此，Turn Bio在斯坦福大学Vittorio Sebastiano博士实验室的表观遗传重编程技术许可的基础上，开发了利用衰老表观遗传重编程逆转细胞老化的创新技术平台ERA™。 ERA™旨在利用特定的转录因子mRNA混合物（如Myc、Oct3/4、Sox2和Klf4等特定蛋白质），通过控制遗传信息从DNA到mRNA的转录速率来打开或关闭基因，从而调控细胞功能并记录细胞年龄的表观基因组的“逆转”，最终恢复细胞的最佳基因表达并促进组织再生。基于该技术平台，Turn Bio能够开发用于干细胞治疗的mRNA药物，以修复受损组织或治疗衰老相关性疾病。据悉，ERA™平台旨在实现安全、快速、高效且可调的重编程过程。通过ERA™平台，Turn Bio能够利用mRNA将转录因子传递至表观基因组。在此过程中，Turn Bio能够严格控制转录因子进入细胞的时间、持续时间和剂量，从而为不同适应症优化mRNA 混合物。例如，Turn Bio可以根据特定组织所获得的益处，添加或去除特定的转录因子。随后，Turn Bio可通过精确地向细胞脉冲式传递转录因子，逐步控制重编程过程，将表观基因组推向更年轻的状态。每次脉冲都会将表观基因组推向更有活力的状态，在稳步恢复细胞功能的同时保护患者。值得一提的是，在研发创新疗法的过程中，Turn Bio发现使用静止期干细胞可以显著帮助修复或替换特定类型的受损组织。其中，静止期干细胞是指处于相对不活跃状态、细胞周期停滞的干细胞。诸多研究证实，它具有低代谢活性、长期存活、抗逆性强等特点，并拥有组织修复和再生、维持组织稳态、疾病治疗潜力等作用。因此，在启用这些干细胞前，必须确保其处于静止状态，以确保它们随时可以被激活、增殖和分化。在此情况下，Turn Bio采用自主研发的“人工生态位（AN™）”技术保护干细胞。AN™技术将干细胞生物学、生物分子材料工程与微加工技术相结合，以生成模拟微环境关键生化或结构方面的新型细胞培养平台。其研究显示，在AN™微环境中培养的肌肉干细胞（MuSC）在移植后表现出更强的植入、组织再生和自我更新潜力。在Turn Bio联用AN™与ERA™技术用于恢复老年小鼠模型干细胞的研究中，研究结果显示，接受联合治疗的老年MuSCs能够恢复与年龄相关的肌肉功能障碍（如肌肉无力），该治疗效果与移植年轻供体的MuSCs所产生的效果相似。重要的是，AN™技术也适用于从其他组织分离出的干细胞的培养。其中，该技术最有可能应用于那些静止状态是维持干细胞功能的必要条件的组织，例如造血系统、肝脏、大脑、毛囊等不同区域和组织中的某些间充质干细胞。除此之外，Turn Bio还克服了药物递送问题，开发了一个新型脂质递送平台 eTurna™。该平台克服了传统脂质载体不稳定性、生物利用度差、溶解性差和体内吸收性差等难题，采用更优化的纳米结构载体，能够安全有效地递送需要不同给药途径的各种药物，并且可以针对特定的组织和细胞进行微调和定位，准确地将药物递送并靶向到特定的组织和细胞。多个管线临床前研究效果显著，核心产品即将进入临床阶段目前，通过专有技术平台，Turn Bio已布局了多个候选管线，包括皮肤科、骨关节炎和软骨损伤、免疫学、眼科、肌肉组织损伤等治疗领域。 Turn Bio产品管线图源：Turn Bio官网目前，TRN-001进展较快。TRN-001是一款拥有独特配方的皮肤抗衰药物，被开发用于治疗毛发和皮肤问题，例如皱纹、脱发、疤痕、炎症、伤口以及晒伤等。临床前研究结果显示，TRN-001可改善皮肤完整性、减少炎症和细胞衰老，并实现毛囊转染，恢复毛囊的毛发生长能力。在骨关节炎和软骨损伤方面，Turn Bio开发了TRN-002。这是一种修复保护性软骨的候选药物，可有效逆转关节损伤，使人们恢复更健康的生活方式。临床前研究结果显示，TRN-002可减少氧化应激和炎症，并改善细胞分裂周期和细胞扩增。在与年龄相关的眼部退行性疾病方面，Turn Bio布局了两大候选产品——TRN-003与TRN-004。其中，TRN -004是一种恢复眼部组织活力的候选药物，包括角膜、角膜缘和结膜上皮细胞以及角膜内皮细胞。临床前研究结果显示 TRN-004可减轻炎症和氧化应激并减少细胞衰老。在肌肉组织损伤方面，Turn Bio正在开发TRN-005。这是一种可恢复肌肉质量和力量，并逆转与年龄相关性疾病的候选药物。临床前研究结果表明，接受TRN-005 治疗后，肌肉组织干细胞生长和分化得到改善，肌肉恢复加快，纤维厚度和力量输出增加。此外，经TRN-005治疗后的肌肉对后期损伤具有更强的抵抗力。值得关注的是，在癌症治疗方面，Turn Bio也布局了相应管线。TRN -010是一款针对T细胞的候选药物。它可以简单地添加到任何CAR-T疗法的制造过程中，并以表观遗传方式重编程患者的T细胞，从而产生更年轻的功能状态，防止T细胞衰竭并产生更高的效力。 Turn Bio表示，恢复T细胞活力和减少细胞衰竭预计将使更多老年患者能够以更低的成本获得CAR-T疗法。临床前研究结果显示，TRN-010治疗可显著提高T细胞增殖和杀死癌细胞的能力，最高可提高5倍。这意味着，对于患者而言，该疗法具有更强的药效和更高的耐受性。与韩国药企达成3亿美元合作，共同开发眼耳疾病新疗法自成立以来，Turn Bio的核心技术与候选产品获得了市场和资本的诸多青睐。目前，Turn Bio已完成了4轮融资，投资者包括Astellas Venture Management、LongeVC、Methuselah Funds等在内的11家知名投资机构和企业。 2024年5月28日，Turn Bio宣布与韩国制药巨头HanAll Biopharma签署了全球独家许可协议，共同开发治疗眼耳疾病的表观遗传重编程疗法。其中，该协议授予HanAll Biopharma利用Turn Bio的ERA™技术研究、开发、制造和商业化眼科和耳科疾病药物的权利。据其表示，首款产品的交易价值可能超过3亿美元。除此之外，韩国制药企业Daewoong Pharmaceutical亦认可了Turn Bio 的技术和研发方向，并通过投资的方式参与了该公司的融资活动，以推动抗衰药物的研发。超10家企业押注细胞重编程，多个产品已进入临床阶段作为延缓衰老的前沿技术之一，细胞重编程目前已成为抗衰领域中最热门的研究之一。近年来，随着技术的不断进步和完善，细胞重编程取得了显著的进展，为延缓衰老、治疗与衰老相关疾病提供了新的可能性。目前，已有多家国内外企业应用细胞重编程方法来开发延缓衰老、治疗年龄相关性疾病的创新疗法，主要包括昕瑞再生、中盛溯源、霍德生物、华夏源细胞工程集团、Retro Bio、Altos Labs、YouthBio Therapeutics、NewLimit、AgeX Therapeutics以及谷歌创立的抗衰生物公司Calico。部分布局细胞重编程企业（不完全统计，企业排名不分先后）图源：公开数据整理，动脉网制图目前，多家公司如昕瑞再生、中盛溯源、艾尔普再生等，已将核心产品推进到临床前或临床研究阶段，验证了细胞重编程技术在抗衰和治疗年龄相关性疾病方面的潜力。与此同时，细胞重编程技术正在不断发展和创新，出现了多种细胞重编程的改进方法，如瞬时重编程、部分重编程等，提高了重编程的效率和安全性。此外，细胞重编程技术不仅应用于组织器官原位再生，还涉及纤维化逆转、免疫疗法等多个领域，未来有望针对不同的疾病类型提供个性化的治疗方案。不过，细胞重编程技术在应用中仍面临着安全性和稳定性等问题。现有研究结果也显示，细胞重编程技术存在致病风险。2013年，西班牙巴塞罗那生物医学研究所Manuel Serrano团队发表论文称，将山中因子应用在小鼠身上，根据重编程发生程度的不同，部分小鼠显示出组织年轻化的迹象，但另一部分小鼠分化出现畸胎瘤。但是，随着技术的不断创新和临床研究的深入，细胞重编程技术的风险或将逐渐降低，细胞重编程抗衰赛道也将迎来全新的发展。未来预计将会有诸多产品应用于临床，为抗衰和治疗年龄相关性疾病带来革命性的变化。如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

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