更新于：2024-11-01

GOX

更新于：2024-11-01

基本信息

别名

2-Hydroxyacid oxidase 1、Glycolate oxidase、glycolate oxidase 1

+ [8]

简介

Broad substrate specificity (S)-2-hydroxy-acid oxidase that preferentially oxidizes glycolate (PubMed:10777549, PubMed:17669354, PubMed:18215067, PubMed:10978532). The glyoxylate produced by the oxidation of glycolate can then be utilized by alanine-glyoxylate aminotransferase for the peroxisomal synthesis of glycine; this pathway appears to be an important step for the detoxification of glyoxylate which, if allowed to accumulate, may be metabolized to oxalate with formation of kidney stones (PubMed:10978532, PubMed:17669354). Can also catalyze the oxidation of glyoxylate, and long chain hydroxyacids such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate, albeit with much lower catalytic efficiency (PubMed:10777549, PubMed:17669354, PubMed:18215067). Active in vitro with the artificial electron acceptor 2,6-dichlorophenolindophenol (DCIP), but O2 is believed to be the physiological electron acceptor, leading to the production of H2O2 (PubMed:10777549, PubMed:17669354, PubMed:18215067, PubMed:10978532). Is not active on L-lactate and 2-hydroxybutanoate (PubMed:10777549).

关联

项与 GOX 相关的药物

Lumasiran sodium

靶点

GOX

作用机制

GOX刺激剂 [+1]

在研机构

Alnylam Netherlands BV [+2]

原研机构

Alnylam Pharmaceuticals, Inc.

在研适应症

原发性高草酸尿症1型 [+1]

非在研适应症

草酸钙肾石病

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2020-11-19

YOLT-203

靶点

GOX

作用机制

GOX抑制剂

在研机构

尧唐（上海）生物科技有限公司

原研机构

尧唐（上海）生物科技有限公司

在研适应症

原发性高草酸尿症1型

非在研适应症-

最高研发阶段早期临床1期

首次获批国家/地区-

首次获批日期1800-01-20

HAO1 inhibitor(Haisco)

HAO1抑制剂(海思科)

靶点

GOX

作用机制

GOX抑制剂

在研机构

西藏海思科制药有限公司

原研机构

西藏海思科制药有限公司

在研适应症

肾结石 [+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 GOX 相关的临床试验

NCT06511349 / Recruiting早期临床1期IIT

Clinical Exploration Study of YOLT-203 in the Treatment of Type 1 Primary Hyperoxaluria (PH1)

This study is a single-arm, open-label, single-dose, dose-escalation trial, aiming to evaluate the safety and tolerability of YOLT-203 in the Chinese population with type 1 primary hyperoxaluria (PH1); and to preliminarily assess the effect of a single dose of YOLT-203 on the plasma oxalate level.
In this study, the maximum screening period of the main study is 60 days, the treatment day is Day 1 (D1), and the safety follow-up period is up to Week 52 after administration. In addition, subjects within the first dose group can voluntarily receive a second treatment with the test drug at the effective dose level.
After the end of the main study, the subjects will undergo long-term follow-up. According to the requirements of the "Technical Guidelines for Long-Term Follow-up Clinical Studies of Gene Therapy Products (Trial)" issued by the CDE, the long-term follow-up is up to 15 years after administration.

开始日期2024-07-12

申办/合作机构

上海交通大学医学院附属仁济医院

NCT06225544 / Recruiting临床2期IIT

Lumasiran in Hyperoxalaemic Patients on Haemodialysis

This study will look at how well a drug that reduced the amount of oxalate in the body works in patients that have kidney disease and need dialysis treatment. People with kidney disease often have higher levels of oxalate in the blood. People with kidney disease are also at higher risk of having heart attacks, heart disease and strokes (these are called cardiovascular diseases). It is thought that high oxalate levels may increase the risk of these diseases. This study will investigate if this medicine can lower the amount of oxalate in the blood of dialysis patients and see if there is any change in the health of their heart. This medicine is already used for people who have high oxalate levels because of a genetic cause and has been used safely for patients on dialysis.
The study will put the participants randomly into either the group getting the study medicine or the group getting a placebo (this will be a solution of saline water). Neither participants not the doctors will know whether the drug or placebo is given until after the end of the study.
At the start of the study all the participants will have an echocardiogram (an ultrasound of the heart) and again 6 months later at the end of the study. We will also take blood tests once a month when the participants come for dialysis.

开始日期2024-04-14

申办/合作机构

Alnylam Pharmaceuticals, Inc.

NCT06225882 / RecruitingN/AIIT

Retrospective and Prospective Follow-up of Patients With Primary Hyperoxaluria Type 1 Treated With Lumasiran in France - DAILY-LUMA

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by mutation in the AGXT gene encoding the hepatic peroxisomal enzyme AGT. Reduced AGT activity results in increased glyoxylate and oxalate production, causing the formation of kidney stones, nephrocalcinosis and renal failure. Clinical trials of Lumasiran have provided information on the efficacy and safety of Lumasiran in the treatment of primary hyperoxaluria type 1. However, they do not provide data on long-term efficacy, safety and patient management. As part of the post-marketing follow-up of Lumasiran, in agreement with the authorities, this study proposes a retrospective and prospective follow-up over 5 years of pediatrics and adults patients treated in France with a standardized clinical, biological and radiological follow-up. The main objective is to monitor the evolution of PH1 parameters and particularly oxaluria before and after treatment.

开始日期2023-01-01

申办/合作机构

Hospices Civils de Lyon

100 项与 GOX 相关的临床结果

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100 项与 GOX 相关的转化医学

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0 项与 GOX 相关的专利（医药）

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2,094

项与 GOX 相关的文献（医药）

2025-02-01·Journal of Colloid and Interface Science

Glucose-fueled cationic nanomotors for promoting the healing of infected diabetic wounds

Article

作者: Lian, Chenxi ; Hu, Junyi ; Xu, Leilei ; Cao, Jingjing ; Guan, Jianguo ; Lin, Jinwei

Hyperglycemia-promoted bacterial infection will seriously exacerbate diabetic wounds, and its current clinical treatments are suffering from the adverse effects associated with off-target, bacterial resistance, and glycemic fluctuation. Herein, we present a kind of glucose-fueled cationic nanomotors capable of remarkably enhancing antibacterial efficacy, and thus expediting diabetic wound healing. The nanomotors have positively charged surfaces, and consist of mesoporous bowl-shaped polydopamine nanoparticles grafted with quaternized polymer brushes and coupled with glucose oxidase (GOx) and catalase (CAT). Stemming from the GOx-CAT cascade reaction in diabetic wound microenvironment, they can perform robust chemotactic motion towards both high glucose regions, where bacteria proliferation predominantly occurs, and elevated H₂O₂ levels, which bacterial metabolism produced. This enables the nanomotors to facilitate targeted migration towards bacteria-rich regions and simultaneous downregulation of glycemic levels, as well as to significantly enhance the electrostatic interaction between antibacterial components and bacteria. Consequently, the nanomotors exhibit amplified contact-killing effects of their attached cationic molecules, leading to an almost 10-fold enhancement in antibacterial efficacy compared to previous counterparts. The in vivo experiments approved that the nanomotors demonstrated the accelerated healing of infected diabetic wounds by S. aureus and biosafety. The results herein provide an insight into the clinical treatment of infected diabetic wounds.

2025-01-01·Talanta

Copper ions coordination-promoted self-assembly of DNA nanoflowers as cascade catalytic nanoreactor for colorimetric biosensor

Article

作者: Qiao, Zhenjie ; Lv, Shuzhen ; Yue, Shuzhen ; Bi, Sai ; Zhang, Xiaoyue ; Shi, Pengfei

The controllable geometry and multifunctionality of DNA nano-bioreactors hold immense promise for disease diagnosis. Herein, a facile rolling circle amplification (RCA)-based crystallization method has been developed for highly efficient self-assembly of three-dimensional (3D) DNA nano-bioreactors, which show excellent cascade catalytic performance by confining bio-enzyme (glucose oxidase (GOx) used in this case) and copper ions (Cu²⁺) in DNA nanoflowers (DNFs) structure. The participation of Cu²⁺ during the self-assembly process not only endows the nano-bioreactors (designated as GOx/Cu@DNFs) with inspiring peroxidase-like activity but also greatly improves the assembly efficiency and yield via the effective coordination between Cu²⁺ and RCA-generated long concatemeric DNAs. The integration of GOx and Cu²⁺ in the constrained flower-like DNA nanomatrices makes for the efficient inter-catalyst communication, resulting in the striking enhancement of biocatalytic cascade activity. Based on the prepared nano-bioreactors, a colorimetric biosensor has been constructed for glucose detection, achieving a wide linear range (2-400 μM) and a low detection limit (0.45 μM). Furthermore, the proposed sensing strategy enables the accurate determination and discrimination of glucose levels in healthy and diabetic sera, delivering gratifying outcomes. Overall, the meticulously crafted cascade nano-bioreactors not only illuminate the design of multifunctional nanomaterials based on RCA, but also expand the conceptual framework of the universal analytical method for determining small molecules with catalytic reactions to generate H₂O₂.

2025-01-01·Colloids and Surfaces B: Biointerfaces

A red cell membrane-camouflaged nanoreactor for enhanced starvation/chemodynamic/ion interference therapy for breast cancer

Article

作者: Zhang, Junhao ; Aharodnikau, Uladzislau E ; Solomevich, Sergey O ; Ren, Luping ; Chen, Nan ; Sun, Yanfang ; Aharodnikau, Uladzislau E. ; Jiang, Guohua ; Yunusov, Khaydar E ; Nie, Lei ; Solomevich, Sergey O. ; Yunusov, Khaydar E.

In this study, a multifunctional Cu-doped CaO₂ nanoreactor loaded with GOx and camouflaged with a folic acid-modified cell membranewas developed for breast cancer treatment. The as-developed composite nanoreactor showed a synergistic effect on calcium overload to damage mitochondria, thus killing tumor cells to achieve ion interference therapy (IIT). The loaded GOx could deplete glucose to "starve" tumor cells. The H₂O₂ released by CaO₂ decomposition and enzyme catalytic reactions from GOx could not only be highly toxic in the tumor microenvironment but also enhance the efficiency of chemodynamic therapy (CDT) with Cu²⁺. The red blood cell membranes modified by folic acid achieved a combination of active targeting and passive targeting, thereby enhancing the targeting ability of the as-prepared multifunctional composite nanoreactor and prolonging its retention time at the tumor sites for more than 48 h.

项与 GOX 相关的新闻（医药）

2024-10-22

·GlobeNewswire-Health Care

Arbor Biotechnologies to Highlight New Preclinical Data Supporting Advancement of Pipeline Programs and Knock-In Applicability of Type V Nucleases at Upcoming Medical and Scientific Meetings

Oral presentation at ASN on lead program, ABO-101 for primary hyperoxaluria type 1 (PH1), supporting in vivo proof of pharmacology. On-track for year-end IND/CTA filing.Oral presentation at ALS One and a poster presentation at ESGCT on lead ALS program ABO-202, highlighting in vivo reversal of ALS-associated STMN2 aberrant splicing and phenotypic outcomes in human motor neurons.Poster presentation at ESGCT demonstrating targeted gene knock-in and broader applicability of type V nuclease platform for monogenic diseases. CAMBRIDGE, Mass., Oct. 22, 2024 (GLOBE NEWSWIRE) -- Arbor Biotechnologies, Inc., a biotechnology company discovering and developing the next generation of genetic medicines, today announced oral and poster presentations on pipeline and early discovery programs at upcoming medical and scientific meetings: American Society of Nephrology (ASN) 2024 Kidney Week Meeting, October 23-27 in San Diego, California31st Annual European Society of Gene and Cell Therapy (ESGCT), October 22-25 in Rome, ItalyALS One 7th Annual ALS Research Symposium, November 13-15, Virtual At ASN Kidney Week, Arbor will present in vivo non-human primate (NHP) proof-of-pharmacology data supporting continued development of ABO-101, its most advanced gene editing therapeutic candidate designed to address primary hyperoxaluria type 1 (PH1) through inactivation of the HAO1 gene in the liver. Arbor is on track to file the IND/CTA for ABO-101 in PH1 by year-end. At the ALS One 7th Annual ALS Research Symposium and at ESGCT, Arbor will detail data on its lead ALS program ABO-202, supporting genetic disruption of STMN2, preventing errors in the processing of its mRNA, and elucidating a path towards proof of concept for a therapeutic CRISPR gene editing approach for the treatment of amyotrophic lateral sclerosis (ALS). The company will also showcase novel data at ESGCT demonstrating targeted gene knock-in at an endogenous promoter achieving equivalent or improved knock-in efficiency when compared to type II nucleases. This data supports the efficiency and breadth of applicability of Arbor’s type V nucleases to monogenic diseases. Details for the presentations are as follows: ASN 2024 Kidney Week:Oral Presentation Title: Development of ABO-101, A Novel Gene Editing Therapy for Primary Hyperoxaluria Type 1 Session Date and Time: Thursday, October 24, 2024, 4:30-6:00pm PDT Location: Room 23, Convention Center Presenter: Winston Yan, MD, PhD Abstract Number: TH-OR88 ESGCT 2024:Poster Title: Gene Editing with a Type V CRISPR-Cas Enzyme Disrupting the Aberrant Splicing of STMN2 as a Potential Treatment for ALS Session Date and Time: Poster Session 1, October 22, 7:30-9:00pm CEST Location: Forum, La Nuvola Presenter: Chee Yeun Chung, PhD Abstract Number: P0327 Poster Title: Targeted Knock-In at the Human TTR Locus Using Type V Nucleases Session Date and Time: Poster Session 3, October 24, 2:00-3:30pm CEST Location: Concourse Level 1 and Mezzanine Concourse, La Nuvola Presenter: Whitney J. French, PhD Abstract Number: P0603 ALS One 7th Annual ALS Research Symposium:Oral Presentation Title: Gene Editing with a Type V CRISPR-Cas Enzyme Disrupting the Aberrant Splicing of STMN2 as a Potential Treatment for ALS Session Date and Time: November 14, 3:40-4:00pm EDT Presenter: Priscilla D. Negraes, PhD About Arbor Biotechnologies, Inc.Arbor BiotechnologiesTM, a next-generation gene editing company based in Cambridge, MA, is advancing a pipeline of novel gene editing therapeutics to address a wide range of genetic conditions - from the ultra-rare to the most common genetic diseases. Our unique suite of optimized gene editors goes beyond the limitations of early editing technologies to unlock access to new gene targets and has fueled a robust pipeline of first-in-class assets focused on diseases of high unmet need. We are rapidly advancing our lead program in primary hyperoxaluria type 1 to the clinic and focusing our research and development efforts on genomic diseases of the liver and CNS for which there are no existing functional cures. For more information, please visit: arbor.bio Media Contact:Peg RusconiDeerfield Groupprusconi@deerfieldgroup.com

基因疗法临床研究

2024-09-16

·佰傲谷BioValley

张锋旗下公司百态，被出售、被合并、被裁员

近日，张锋旗下的一家名为Arbor Biotechnologies的公司正在削减其早期发现工作，并进行了相应裁员。 Arbor Biotechnologies是一家基因编辑酶开发公司，成立于2016年，由张锋、David Walt、David Scott以及Winston Yan联合创办。 2017年Arbor走出隐匿模式，获得1560万美元A轮融资，2021年完成2.15亿美元的B轮融资。 Arbor旨在通过机器学习/人工智能技术来开发新的基因编辑器。截至目前，公司已开发了9种基因编辑器，覆盖90%以上的基因组，并且还发现了超60多种核酸酶家族和70多种CRISPR转座酶，如DNA核酸酶（Cas12h，Cas12i）、RNA核酸酶（Cas13d，Cas12g，III-E型）和转座酶Tn7-Cas12等。基于其CRISPR基因编辑技术，Arbor分别在2021年8月和2022年2月，与Vertex和博雅辑因达成了授权合作。目前官网公开的有5条管线，尚无管线进入临床。首发管线是一种针对原发性高草酸尿症（PH）的体内基因编辑疗法ABO-101，目前正在IND enabling阶段。在2024 ASGCT年会上，Arbor公布了BO-101的临床前数据。在非人灵长类动物（NHP）中，BO-101对HAO1基因（乙醇酸氧化酶编码基因）有效的体内编辑，多次给药具有良好的耐受性。Arbor预计在今年递交ABO-101的IND申请。联合创立9家公司作为基因编辑领域的大牛，围绕在CRISPR基因编辑技术的探索成果，张锋同样已建立起了一个庞大的基因编辑版图。至今以来，张锋作为创始人或者联合创始人至少创立了9家公司，包括Editas Medicine、Arbor Biotechnologies、Pairwise Plants、Beam Therapeutics、Sherlock Biosciences、Proof Diagnostics、Aera Therapeutics、Moonwalk Biosciences、Serendipity Biosciences，这些公司涵盖了CRISPR编辑技术在基因编辑、碱基编辑、分子诊断、农业科技等各个领域的应用。然而，在充满挑战的融资环境下，这些公司也有不同的发展境遇，有的被出售、有的裁员重组、有的被合并。在去年，张锋旗下三家公司Editas Medicine、Beam Therapeutics、Aera Therapeutics都加入了裁员大军，进行了重大的战略调整，管线收缩、收缩队伍，延长现金跑道。作为张锋创办的第一家公司，Editas的处境是最令人堪忧的。在去年采取裁员措施时（2023年9月30日），公司现金流已经告急，仅剩8250万美元（现金及其等价物）。对公司造成巨大打击的是领先管线EDIT-101的失败，这是全球首个在人体内给药的CRISPR基因组编辑药物，也曾是Editas最快的管线，不过因为Ⅰ/Ⅱ期临床数据不佳而被终止开发。自此，Editas也失去基因编辑领域的领先地位，进展已经落后于与其齐平的竞争对手CRISPR Therapeutics。为此，Editas进行了战略和架构的重大调整，停止对EDIT-101、EDIT-103、EDIT-202等多款管线的内部开发（寻求对外合作）。事实上，相较Editas而言，Beam的现金流并算是比较充足了，去年统计的时候现金、现金等价物以及有价证券还有约10亿美元（截至2023年9月30日），不过公司碱基编辑管线推进较慢，患者入组非常困难，进行技术转化验证是一个长期消耗战，后续需要不少资金支撑。为了储备足够资金，抵抗寒冬的威胁，Beam也加入了裁员大军（裁员比例20%），同时也对管线也进行了大调整，包括暂停对BEAM-201内部开发，优先推进BEAM-101、BEAM-302等管线。加入裁员队列的不止这些最早成立的一批公司，才走出隐身模式的新公司Aera Therapeutics也采取了裁员行动。 Aera Therapeutics是2023年完成1.93亿美元的A轮和B轮融资后得到业界关注。但是这家才拿到融资一年，管线都没搭建起来就也启动了裁员措施。 2024年1月5日，Aera宣布裁员25%。根据公司所述，部分新型基因编辑酶开发人员已经被裁。裁员的原因也和Beam相同，出于对未来融资环境的担忧，公司的现金流并不急迫。裁员后，公司将把投资重点放在新型交付平台的开发上，进一步扩大现金跑道。张锋首家被出售的的公司Proof Diagnostics是一家为新冠提供体外诊断测试的生物技术公司，在今年1月被合成生物学巨头Ginkgo Bioworks收入麾下。除了对外出售之外，张锋旗下的公司还进行了合并。今年5月，Arbor收购了张锋旗下另一家公司Serendipity Biosciences，具体财务细节双方并未公布。本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

基因疗法临床申请

2024-09-13

·Endpoints

Arbor Biotechnologies cuts early-stage discovery work, lays off staff

Arbor Biotechnologies is trimming its early-stage discovery work, leading to layoffs in the group. The move was confirmed by an Arbor spokesperson, with CEO Devyn Smith saying in a statement to Endpoints News on Friday that the company is prioritizing clinical-stage investments. “We are keenly focused on delivering new medicines and will strategically shift resources and efforts accordingly to support the transition to a clinical-stage company,” Smith said. The company did not disclose how many employees were laid off. The gene editing company was born out of the lab of CRISPR scientist Feng Zhang and launched in 2018 with a $15.6 million Series A. As the potential of gene editing grew, the company attracted more investors, closing a $215 million Series B round in 2021. The financing was co-led by Temasek, Ally Bridge Group, and TCG Crossover. The company said then that the capital would be used not only to advance programs into the clinic, but also to continue investing in a “novel discovery engine to develop the next generation of gene editing technology.” Earlier this year, Arbor bought another Zhang-founded biotech , Serendipity Bioscience, though financial details about the acquisition were undisclosed. The purchase allowed Arbor access to additional gene editing technology based around enzymes that are smaller than Cas9. The hope is that these could be used in different delivery methods that can’t accommodate the Cas9 protein. Arbor’s lead program, ABO-101, is currently in IND-enabling studies as a treatment for primary hyperoxaluria type 1 (PH1), a condition marked by abnormally high levels of oxalate in urine. This can increase the risk of certain kinds of kidney stones and in severe cases can cause kidney failure. Arbor presented preclinical data of ABO-101 in May, finding that it had “highly specific targeting of the HAO1 gene” in non-human primates that produced a “therapeutically relevant reduction in urinary oxalate.” Another liver-aimed program to treat transthyretin amyloidosis (ATTR) remains in the discovery stage. Three other CNS programs are also listed in the program, two of which are in the lead optimization phase. All three are being developed as potential treatments for amyotrophic lateral sclerosis.

并购基因疗法