Molecular Therapy最新文献

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Adipocyte cell therapy targeting bone morphogenetic protein signaling alleviates fibroadipose tissue deposition in secondary lymphedema. 靶向骨形态发生蛋白信号通路的脂肪细胞治疗减轻继发性淋巴水肿的纤维脂肪组织沉积。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-22 DOI: 10.1016/j.ymthe.2025.09.034
Ziyu Chen,Mengfan Wu,Samerender Nagam Hanumantharao,Pratik Koirala,Soheila Ali Akbari Ghavimi,Ashley E Siegel,Chang Liu,Erin Taylor,Justin Broyles,Indranil Sinha,Vicki Rosen,Shailesh Agarwal
{"title":"Adipocyte cell therapy targeting bone morphogenetic protein signaling alleviates fibroadipose tissue deposition in secondary lymphedema.","authors":"Ziyu Chen,Mengfan Wu,Samerender Nagam Hanumantharao,Pratik Koirala,Soheila Ali Akbari Ghavimi,Ashley E Siegel,Chang Liu,Erin Taylor,Justin Broyles,Indranil Sinha,Vicki Rosen,Shailesh Agarwal","doi":"10.1016/j.ymthe.2025.09.034","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.034","url":null,"abstract":"Secondary lymphedema is a chronic disease affecting an isolated limb following lymph node resection for cancer treatment. Management options are limited and onerous, leading to near-universal progression to subcutaneous fibroadipose tissue deposition. Here, we identify bone morphogenetic protein ligands (BMPs) as mediators of fibroadipose tissue deposition through in vitro experiments with human lymphedema fluid and BMP-specific inhibitor. Systemic in vivo delivery of BMP inhibitor reduces fibroadipose tissue deposition in a mouse model of hindlimb secondary lymphedema. Considering systemic delivery may be undesirable for an anatomically-isolated disease, we engineered a cell therapy using purified adipocytes, aiming for clinical translation in a resource- and time- constrained environment requiring only mechanical manipulation. We then devised a strategy for gene delivery into adipocytes and verified the secretion of the recombinant peptide inhibitor of BMP ligands. Upon in vivo delivery of the engineered adipocytes, we verified secretion of the BMP inhibitor and a reduction in fibroadipose tissue deposition in the mice hindlimb. Our findings highlight BMPs as signaling mediators for fibroadipose tissue deposition and provide a blueprint for a cell therapy using genetically-modified adipocytes for local drug delivery. This approach may be in a point-of-care strategy and potentially be amenable to various conditions.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"18 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127083","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
Chimeric Enzymes Enhance Treatment Potential For Globoid Cell Leukodystrophy through Hematopoietic Stem Cell Gene Therapy. 嵌合酶通过造血干细胞基因治疗增强对白细胞营养不良的治疗潜力。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-22 DOI: 10.1016/j.ymthe.2025.09.030
Federica Cascino,Alessandra Ricca,Ilaria Picciotti,Erika Valeri,Giulia Unali,Veronica Saporito,Marta Freschi,Francesco Morena,Sabata Martino,Anna Kajaste-Rudnitski,Angela Gritti
{"title":"Chimeric Enzymes Enhance Treatment Potential For Globoid Cell Leukodystrophy through Hematopoietic Stem Cell Gene Therapy.","authors":"Federica Cascino,Alessandra Ricca,Ilaria Picciotti,Erika Valeri,Giulia Unali,Veronica Saporito,Marta Freschi,Francesco Morena,Sabata Martino,Anna Kajaste-Rudnitski,Angela Gritti","doi":"10.1016/j.ymthe.2025.09.030","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.030","url":null,"abstract":"Globoid cell leukodystrophy (GLD) is a fatal lysosomal storage disorder caused by a deficiency in the β-galactosylceramidase (GALC) enzyme, leading to severe demyelination and neurodegeneration, and often death before the age of two. Hematopoietic stem/progenitor cell transplantation (HSPC-T) has limited efficacy due to inadequate GALC delivery to the central and peripheral nervous systems (CNS, PNS) and associated risks. In vivo gene therapy (GT) using adeno-associated viral vectors shows promise, but safety concerns persist. This research presents a strategy using lentiviral vector (LV)-mediated ex vivo HSPC-GT with a chimeric GALC enzyme that incorporates peptides from alpha-L-iduronidase (IDUA) and apolipoprotein E II (APO) to enhance expression and blood-brain barrier penetration. The chimeric IDUAsp.GALC.APO enzyme exhibited superior production and secretion compared to native GALC and previous chimeric variants in LV-transduced HSPCs, resulting in improved cross-correction and normalization of GALC activity in GLD neural cells. Proof-of-concept studies demonstrated effective enzyme production, secretion, and cross-correction capability of macrophages from GLD patients. In vivo results showed stable gene marking, sustained enzyme production, and efficient delivery of the chimeric GALC in affected organs, including the CNS and PNS. These findings highlight the potential of HSPC-GT using chimeric GALC enzymes as an innovative therapeutic approach for treating GLD.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"40 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127136","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
Pluripotent stem cell-based therapy toward the clinic for muscular dystrophy. 以多能干细胞为基础的肌萎缩症临床治疗。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-22 DOI: 10.1016/j.ymthe.2025.09.014
Helena Escobar
{"title":"Pluripotent stem cell-based therapy toward the clinic for muscular dystrophy.","authors":"Helena Escobar","doi":"10.1016/j.ymthe.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.014","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"24 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127084","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
A STING agonist potentiates C1 lipidoid-based mRNA cancer vaccine through promoting TNF-α secretion in vivo. STING激动剂通过促进体内TNF-α分泌来增强基于C1类脂质mRNA的癌症疫苗。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-22 DOI: 10.1016/j.ymthe.2025.09.032
Hongxia Zhang,Yang Lin,Liying Wang,Lei Cui,Zining Wang,Xinru You,Chunyuan Xie,Huanling Zhang,Yongxiang Liu,Mengyun Li,Xiaojuan Wang,Jun Wu,Xiaojun Xia
{"title":"A STING agonist potentiates C1 lipidoid-based mRNA cancer vaccine through promoting TNF-α secretion in vivo.","authors":"Hongxia Zhang,Yang Lin,Liying Wang,Lei Cui,Zining Wang,Xinru You,Chunyuan Xie,Huanling Zhang,Yongxiang Liu,Mengyun Li,Xiaojuan Wang,Jun Wu,Xiaojun Xia","doi":"10.1016/j.ymthe.2025.09.032","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.032","url":null,"abstract":"Intracellular delivery of antigen-encoding mRNA-based vaccine has shown great potential in the treatment of cancer and infectious diseases. We previously developed a minimalist cancer nanovaccine using C1 lipidoid nanoparticle with self-adjuvant activity, which markedly improve mRNA delivery and antigen presentation through TLR4 signaling activation. Although C1-mRNA nanovaccine induced strong antitumor efficiency in prophylactic and therapeutic settings, it could not eliminate tumors with low immunogenicity. To further improve the therapeutic efficacy of mRNA vaccine, we screened several innate immune receptor agonists and identified STING agonist as an effective adjuvant for C1-mRNA vaccine, which could effectively promote the production of type I interferon and proinflammatory cytokines including IL-12 and TNF-α in dendritic cells. Such C1-mRNA cancer vaccine adjuvanted with STING agonist effectively promoted antigen presentation in dendritic cells and enhanced T cell activation and exhibited strong antitumor activity on tumor models. Mechanistically, this mRNA vaccine showed improved antitumor efficacy largely depending on STING protein expression in dendritic cells and TNF-α induction in vivo, while type I interferon or IL-12 induction seemed dispensable. Together, by optimizing the antitumor efficacy of C1-mRNA cancer vaccine with STING agonist, this work provides a potential mRNA cancer vaccine platform for treating a wide range of tumor types.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"40 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127163","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
To c or not to c-KIT?: High toxicity and modest efficacy in CD117-directed CAR T cell therapy. 去c还是不去c- kit ?cd117靶向CAR - T细胞治疗的高毒性和中等疗效。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-20 DOI: 10.1016/j.ymthe.2025.09.021
Isaac Gannon,Claire Roddie,Alex Rampotas
{"title":"To c or not to c-KIT?: High toxicity and modest efficacy in CD117-directed CAR T cell therapy.","authors":"Isaac Gannon,Claire Roddie,Alex Rampotas","doi":"10.1016/j.ymthe.2025.09.021","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.021","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"59 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103383","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
Long COVID: Is mitochondria the target? 长冠:线粒体是目标吗?
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-20 DOI: 10.1016/j.ymthe.2025.09.019
Bernat Soria,Etelvina Andreu,Aitor Gonzaga
{"title":"Long COVID: Is mitochondria the target?","authors":"Bernat Soria,Etelvina Andreu,Aitor Gonzaga","doi":"10.1016/j.ymthe.2025.09.019","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.019","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"33 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103384","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
A sophisticated approach to targeting TERT activity in DLBCL. 靶向DLBCL中TERT活性的复杂方法。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-20 DOI: 10.1016/j.ymthe.2025.09.022
Giorgio Inghirami,Leandro Cerchietti
{"title":"A sophisticated approach to targeting TERT activity in DLBCL.","authors":"Giorgio Inghirami,Leandro Cerchietti","doi":"10.1016/j.ymthe.2025.09.022","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.022","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"17 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103382","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
Mobilization meets antibody conditioning: A path toward safer engraftment. 动员符合抗体条件:通往更安全植入的途径。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-20 DOI: 10.1016/j.ymthe.2025.09.018
M Kyle Cromer
{"title":"Mobilization meets antibody conditioning: A path toward safer engraftment.","authors":"M Kyle Cromer","doi":"10.1016/j.ymthe.2025.09.018","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.018","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"87 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103386","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
EROdicating arterial thrombosis with a novel endoplasmic reticulum oxidoreductase 1α inhibitor. 一种新型内质网氧化还原酶1α抑制剂消除动脉血栓形成。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-19 DOI: 10.1016/j.ymthe.2025.09.012
Timur O Yarovinsky,Anish V Sharda,John Hwa
{"title":"EROdicating arterial thrombosis with a novel endoplasmic reticulum oxidoreductase 1α inhibitor.","authors":"Timur O Yarovinsky,Anish V Sharda,John Hwa","doi":"10.1016/j.ymthe.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.012","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"56 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093560","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
Computational optimization of chimeric antigen receptor. 嵌合抗原受体的计算优化。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-19 DOI: 10.1016/j.ymthe.2025.09.015
Taisuke Kondo,Chisato Umehara,Yuki Kagoya
{"title":"Computational optimization of chimeric antigen receptor.","authors":"Taisuke Kondo,Chisato Umehara,Yuki Kagoya","doi":"10.1016/j.ymthe.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.015","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"11 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093517","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
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