Molecular Therapy最新文献_第2页

The impact of revised regenerative medicine regulations on unapproved gene therapies in Japan. 日本修订再生医学法规对未经批准的基因疗法的影响。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-02-25 DOI: 10.1016/j.ymthe.2025.02.018

Yuichiro Ukon, Satoshi Hosoya, Kazuki Morita, Eisuke Minegishi, Jun Sugihara

引用次数: 0

GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice. GDF11在载脂蛋白e缺失小鼠中保护内皮损伤并减少动脉粥样硬化病变形成。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-05-19 DOI: 10.1016/j.ymthe.2025.04.014

Wen Mei, Guangda Xiang, Yixiang Li, Huan Li, Lingwei Xiang, Junyan Lu, Lin Xiang, Jing Dong, Min Liu

引用次数: 0

Effect of immunoadsorption on clinical presentation and immune alterations in COVID-19-induced and/or aggravated ME/CFS. 免疫吸附对covid -19诱导和/或加重ME/CFS临床表现和免疫改变的影响

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-01-10 DOI: 10.1016/j.ymthe.2025.01.007

Moritz Anft, Lea Wiemers, Kamil S Rosiewicz, Adrian Doevelaar, Sarah Skrzypczyk, Julia Kurek, Sviatlana Kaliszczyk, Maximilian Seidel, Ulrik Stervbo, Felix S Seibert, Timm H Westhoff, Nina Babel

{"title":"Effect of immunoadsorption on clinical presentation and immune alterations in COVID-19-induced and/or aggravated ME/CFS.","authors":"Moritz Anft, Lea Wiemers, Kamil S Rosiewicz, Adrian Doevelaar, Sarah Skrzypczyk, Julia Kurek, Sviatlana Kaliszczyk, Maximilian Seidel, Ulrik Stervbo, Felix S Seibert, Timm H Westhoff, Nina Babel","doi":"10.1016/j.ymthe.2025.01.007","DOIUrl":"10.1016/j.ymthe.2025.01.007","url":null,"abstract":"Autoantibodies (AABs) are currently being investigated as causative or aggravating factors during post-COVID. In this study, we analyze the effect of immunoadsorption therapy on symptom improvement and the relationship with immunological parameters in post-COVID patients exhibiting symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) induced or aggravated by an SARS-CoV-2 infection. This observational study includes 12 post-COVID patients exhibiting a predominance of ME/CFS symptoms alongside increased concentrations of autonomic nervous system receptor (ANSR) autoantibodies and neurological impairments. We found that following immunoadsorption therapy, the ANSR AABs were nearly eliminated from the patients' blood. The removal of immunoglobulin G antibodies was accompanied by a decrease of pro-inflammatory cytokines including interleukin (IL)-4, IL-2, IL-1β, tumor necrosis factor, and IL-17A serum levels, and a significant reduction of soluble spike protein. Notably, a strong positive correlation between pro-inflammatory cytokines and ASNR-AABs β1, β2, M3, and M4 was observed in spike protein-positive patients, whereas no such correlation was evident in spike protein-negative patients. Thirty days post-immunoadsorption therapy, patients exhibited notable improvement in neuropsychological function and a modest but statistically significant amelioration of hand grip strength was observed. However, neither self-reported symptoms nor scores on ME/CFS questionnaires showed a significant improvement and a rebound of the removed proteins occurring within a month.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2886-2899"},"PeriodicalIF":12.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low-level shRNA Cytotoxicity Can Contribute to MYC-induced Hepatocellular Carcinoma in Adult Mice. 低水平shRNA细胞毒性可促进myc诱导的成年小鼠肝细胞癌。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-04-10 DOI: 10.1016/j.ymthe.2025.03.036

Shelly Beer, David I Bellovin, Joyce S Lee, Kimberly Komatsubara, Lora S Wang, Huishan Koh, Kathleen Börner, Theresa A Storm, Corrine R Davis, Mark A Kay, Dean W Felsher, Dirk Grimm

引用次数: 0

Efficient gene delivery admitted by small metabolites specifically targeting astrocytes in the mouse brain. 小鼠脑内星形胶质细胞特异性小代谢物的高效基因传递。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-05-14 DOI: 10.1016/j.ymthe.2025.05.015

Haibin Zhou, Jiajing Dai, Dong Li, Luyao Wang, Meng Ye, Xiaoling Hu, Joseph LoTurco, Ji Hu, Wenzhi Sun

引用次数: 0

The rise of cochlear gene therapy. 人工耳蜗基因疗法的崛起

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2024-11-08 DOI: 10.1016/j.ymthe.2024.11.012

Lukas D Landegger, Ellen Reisinger, François Lallemend, Steffen R Hage, Dirk Grimm, Christopher R Cederroth

引用次数: 0

Managing allorejection in off-the-shelf CAR-engineered cell therapies. 管理现成 CAR 工程细胞疗法中的异体排斥反应。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2024-11-26 DOI: 10.1016/j.ymthe.2024.11.035

Yan-Ruide Li, Ying Fang, Siyue Niu, Yuning Chen, Zibai Lyu, Lili Yang

{"title":"Managing allorejection in off-the-shelf CAR-engineered cell therapies.","authors":"Yan-Ruide Li, Ying Fang, Siyue Niu, Yuning Chen, Zibai Lyu, Lili Yang","doi":"10.1016/j.ymthe.2024.11.035","DOIUrl":"10.1016/j.ymthe.2024.11.035","url":null,"abstract":"Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has revolutionized the treatment of various diseases, including cancers and autoimmune disorders. However, all US Food and Drug Administration (FDA)-approved CAR-T cell therapies are autologous, and their widespread clinical application is limited by several challenges, such as complex individualized manufacturing, high costs, and the need for patient-specific selection. Allogeneic off-the-shelf CAR-engineered cell therapy offers promising potential due to its immediate availability, consistent quality, potency, and scalability in manufacturing. Nonetheless, significant challenges, including the risks of graft-versus-host disease (GvHD) and host-cell-mediated allorejection, must be addressed. Strategies such as knocking out endogenous T cell receptors (TCRs) or using alternative therapeutic cells with low GvHD risk have shown promise in clinical trials aimed at reducing GvHD. However, mitigating allorejection remains critical for ensuring the long-term sustainability and efficacy of off-the-shelf cell products. In this review, we discuss the immunological basis of allorejection in CAR-engineered therapies and explore various strategies to overcome this challenge. We also highlight key insights from recent clinical trials, particularly related to the sustainability and immunogenicity of allogeneic CAR-engineered cell products, and address manufacturing considerations aimed at minimizing allorejection and optimizing the efficacy of this emerging therapeutic approach.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2368-2390"},"PeriodicalIF":12.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene therapy in China: From a clinician's perspective. 基因治疗在中国：从临床医生的角度看基因治疗。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-01-24 DOI: 10.1016/j.ymthe.2025.01.018

Xiaole Wang, Jing Peng

引用次数: 0

Pilocytic astrocytoma in a child with spinal muscular atrophy treated with onasemnogene abeparvovec. Onasemnogene abparvovec治疗脊髓性肌萎缩症儿童的毛细胞星形细胞瘤。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-02-15 DOI: 10.1016/j.ymthe.2025.02.025

Dorothea Holzwarth, Gabriele Calaminus, Johannes Friese, Thomas Sejersen, Hildegard Büning, Philipp John-Neek, Antonella Lucía Bastone, Michael Rothe, Keith Mansfield, Silvana Libertini, Valérie Dubost, Brent Kuzmiski, Iulian Alecu, Ivan Labik, Janbernd Kirschner

{"title":"Pilocytic astrocytoma in a child with spinal muscular atrophy treated with onasemnogene abeparvovec.","authors":"Dorothea Holzwarth, Gabriele Calaminus, Johannes Friese, Thomas Sejersen, Hildegard Büning, Philipp John-Neek, Antonella Lucía Bastone, Michael Rothe, Keith Mansfield, Silvana Libertini, Valérie Dubost, Brent Kuzmiski, Iulian Alecu, Ivan Labik, Janbernd Kirschner","doi":"10.1016/j.ymthe.2025.02.025","DOIUrl":"10.1016/j.ymthe.2025.02.025","url":null,"abstract":"Spinal muscular atrophy (SMA) is a severe neuromuscular disease, leading to progressive muscle weakness and potentially early mortality if untreated. Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (rAAV9)-based gene therapy that has demonstrated improvements in survival and motor function for SMA patients. Here, we present a case of a patient diagnosed with a grade 1 pilocytic astrocytoma at the age of 2 years, approximately 8 months after onasemnogene abeparvovec treatment. Although vector genomes delivered by rAAVs persist primarily as episomes, rare integration events have been linked to tumor formation in neonate murine models. Therefore, we investigated the presence and possible integration of onasemnogene abeparvovec in formalin-fixed paraffin embedded (FFPE) and frozen tumor samples. In situ hybridization demonstrated variable transduction levels in individual tumor cells, while droplet digital PCR measured an average vector copy number ranging from 0.7 to 4.9 vector genomes/diploid genome. Integration site analysis identified a low number of integration sites that were not conserved between technical replicates, nor between FFPE and frozen samples, indicating that cells hosting integrating vector genomes represented a minority in the overall cell population. Thus, molecular analysis of the tumor tissue suggests that tumorigenesis was causally independent of the administration of onasemnogene abeparvovec.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2842-2850"},"PeriodicalIF":12.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lyophilized apoptotic vesicles improve hemostasis and bone regeneration in traumatic patients with impacted third molar extraction. 冻干细胞凋亡小泡改善创伤性出血患者阻生第三磨牙拔牙后的止血和骨再生。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-06-04 Epub Date: 2025-02-22 DOI: 10.1016/j.ymthe.2025.02.033

Yexiang Jiang, Xuemeng Li, Ruoxin Huang, Fangcao Lei, Lingzhi Li, Bo Yang, Wenfeng Zen, Huagen Tan, Yun Huang, Jing Hu, Yasha Xiong, Zhiyuan Wang, Zetao Chen, Lili Chen, Songtao Shi, Xueli Mao

{"title":"Lyophilized apoptotic vesicles improve hemostasis and bone regeneration in traumatic patients with impacted third molar extraction.","authors":"Yexiang Jiang, Xuemeng Li, Ruoxin Huang, Fangcao Lei, Lingzhi Li, Bo Yang, Wenfeng Zen, Huagen Tan, Yun Huang, Jing Hu, Yasha Xiong, Zhiyuan Wang, Zetao Chen, Lili Chen, Songtao Shi, Xueli Mao","doi":"10.1016/j.ymthe.2025.02.033","DOIUrl":"10.1016/j.ymthe.2025.02.033","url":null,"abstract":"Uncontrollable bleeding and tissue defects caused by trauma are significant clinical issues. Apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs) have shown promise for hemostasis and tissue regeneration, but their clinical safety and efficacy remain unverified. We investigated the procoagulant and regenerative function of lyophilized MSC-derived apoVs (MSC-apoVs) using in vitro experiments and in vivo rat models. In addition, we conducted a double-blind, randomized, self-controlled clinical trial to evaluate the safety and efficiency of lyophilized MSC-apoVs for hemostasis and bone regeneration following extraction of impacted mandibular third molars. We show that lyophilized MSC-apoVs maintain their procoagulant and regenerative functions after storage at 4°C for 3 months and upregulate tripartite motif containing 71 to activate the extracellular signal-regulated kinase signaling pathway. Furthermore, among the 43 enrolled subjects, 39 patients completed all follow-ups and 4 patients were lost to contact. All 39 patients tolerated MSC-apoVs well, with no serious adverse events or abnormal blood test results observed. The MSC-apoV group exhibited shortened hemostatic time and accelerated alveolar bone regeneration compared with the control group. This is the first clinical study to demonstrate that apoVs are safe, well tolerated, and effective as a cell-free biological therapy for hemostasis and bone regeneration.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2931-2944"},"PeriodicalIF":12.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0