Molecular Therapy最新文献

Promotion or inhibition? This is a question in gene editing.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-21 DOI: 10.1016/j.ymthe.2025.01.014

Li-Kuang Tsai, Renzhi Han, Dongshan Yang, Y Eugene Chen, Jifeng Zhang, Jie Xu

引用次数: 0

Low-inflammatory lipid nanoparticles facilitate safe mRNA vaccination against influenza virus infection.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-21 DOI: 10.1016/j.ymthe.2025.01.020

Yuehua Xu, Guangxi Zhai, Da-Peng Yang, Gang Chen

引用次数: 0

Orchestrating cytosolic access: The partnership of cationic lytic peptide L17E and potassium channel KCa3.1.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-21 DOI: 10.1016/j.ymthe.2025.01.019

Keykavous Parang

引用次数: 0

RNA and epigenetic editing: The new frontier in gene and cell therapy.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-21 DOI: 10.1016/j.ymthe.2025.01.017

Federico Avila-Moreno, Paloma H Giangrande

引用次数: 0

Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease. 玻璃体连接蛋白调节慢性阻塞性肺疾病的肺组织重塑和肺气肿。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-21 DOI: 10.1016/j.ymthe.2025.01.032

Gang Liu, Alan C Hsu, Silke Geirnaert, Christine Cong, Prema M Nair, Sj Sijie Shen, Jacqueline Marshall, Tatt Jhong Haw, Michael Fricker, Ashleigh M Philp, Nicole G Hansbro, Stelios Pavlidis, Yike Guo, Janette K Burgess, Leandro Castellano, Antonio Ieni, Gaetano Caramori, Brain G Oliver, K Fan Chung, Ian M Adcock, Darryl A Knight, Francesca Polverino, Ken Bracke, Peter A Wark, Philip M Hansbro

{"title":"Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease.","authors":"Gang Liu, Alan C Hsu, Silke Geirnaert, Christine Cong, Prema M Nair, Sj Sijie Shen, Jacqueline Marshall, Tatt Jhong Haw, Michael Fricker, Ashleigh M Philp, Nicole G Hansbro, Stelios Pavlidis, Yike Guo, Janette K Burgess, Leandro Castellano, Antonio Ieni, Gaetano Caramori, Brain G Oliver, K Fan Chung, Ian M Adcock, Darryl A Knight, Francesca Polverino, Ken Bracke, Peter A Wark, Philip M Hansbro","doi":"10.1016/j.ymthe.2025.01.032","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.01.032","url":null,"abstract":"Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in COPD is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1, uPAR) that induced collagen and airway remodeling. In the parenchyma, VTN levels were decreased, uPA signalling pathway differentially altered and collagen reduced in lung fibroblasts from human and lung parenchyma in experimental COPD. Vtn inhibition with siRNA in mouse fibroblasts altered uPA signalling increased matrix metalloproteinase-12, and reduced collagen, whereas over-expression restored collagen production after CS extract challenge. Vtn-/- and Vtn siRNA-treated mice had exaggerated inflammation, emphysema and impaired lung function compared to controls with CS-induced COPD. Restoration of VTN in the parenchyma may be a therapeutic option for emphysema and COPD.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007659","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

SHIV fights back to evade destruction by eCD4-Ig but not without suffering debilitating wounds.

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-21 DOI: 10.1016/j.ymthe.2025.01.001

Eric J Arts

引用次数: 0

Treating genetic blood disorders in the era of CRISPR-mediated genome editing. 在crispr介导的基因组编辑时代治疗遗传性血液病。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-01-17 DOI: 10.1016/j.ymthe.2025.01.031

Alhomidi Almotiri,Ahmed Abogosh,Ali Abdelfattah,Dalya Alowaisy,Neil P Rodrigues

引用次数: 0

ENHANCED RESTORATION OF VISUAL CODE AFTER TARGETING ON BIPOLAR CELLS COMPARED TO RETINAL GANGLION CELLS WITH OPTOGENETIC THERAPY. 与光基因治疗视网膜神经节细胞相比，靶向双极细胞后视觉密码的恢复增强。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-17 DOI: 10.1016/j.ymthe.2025.01.030

Jessica Rodgers, Steven Hughes, Aghileh S Ebrahimi, Annette E Allen, Riccardo Storchi, Moritz Lindner, Stuart N Peirson, Tudor C Badea, Mark W Hankins, Robert J Lucas

{"title":"ENHANCED RESTORATION OF VISUAL CODE AFTER TARGETING ON BIPOLAR CELLS COMPARED TO RETINAL GANGLION CELLS WITH OPTOGENETIC THERAPY.","authors":"Jessica Rodgers, Steven Hughes, Aghileh S Ebrahimi, Annette E Allen, Riccardo Storchi, Moritz Lindner, Stuart N Peirson, Tudor C Badea, Mark W Hankins, Robert J Lucas","doi":"10.1016/j.ymthe.2025.01.030","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.01.030","url":null,"abstract":"Optogenetic therapy is a promising vision restoration method where light sensitive opsins are introduced to the surviving inner retina following photoreceptor degeneration. The cell type targeted for opsin expression will likely influence the quality of restored vision. However, a like-for-like pre-clinical comparison of visual responses evoked following equivalent opsin expression in the two major targets, ON bipolar (ON BCs) or retinal ganglion cells (RGCs), is absent. We address this deficit by comparing stimulus-response characteristics at single unit resolution in the retina and dorsal lateral geniculate nucleus (dLGN) of retinally degenerate mice genetically engineered to express the opsin ReaChR in Grm6- or Brn3c-expressing cells (ON BC vs RGCs respectively). For both targeting strategies, we find ReaChR-evoked responses have equivalent sensitivity and can encode contrast across different background irradiances. Compared to ON BCs, targeting RGCs decreased response reproducibility and resulted in more stereotyped responses with reduced diversity in response polarity, contrast sensitivity and temporal frequency tuning. Recording ReaChR-driven responses in visually intact retinas confirmed that RGC-targeted ReaChR expression disrupts visual feature selectivity of individual RGCs. Our data show that while both approaches restore visual responses with impressive fidelity, ON BC targeting produces a richer visual code closer to that of wildtype mice.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008782","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

Transforming Bacterial Pathogens into Wonder Tools in Cancer Immunotherapy. 将细菌病原体转化为癌症免疫治疗的神奇工具。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-01-17 DOI: 10.1016/j.ymthe.2025.01.029

Amal Senevirathne,Khristine Kaith S Lloren,Ram Prasad Aganja,Jun Kwon,John Hwa Lee

{"title":"Transforming Bacterial Pathogens into Wonder Tools in Cancer Immunotherapy.","authors":"Amal Senevirathne,Khristine Kaith S Lloren,Ram Prasad Aganja,Jun Kwon,John Hwa Lee","doi":"10.1016/j.ymthe.2025.01.029","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.01.029","url":null,"abstract":"Cancer immunotherapy has revolutionized cancer treatment due to its precise, target-specific approach compared to conventional therapies. However, treating solid tumors remains challenging as these tumors are inherently immunosuppressive, and their tumor microenvironment (TME) often limits therapeutic efficacy. Interestingly, certain bacterial species offer a promising alternative by exhibiting an innate ability to target and proliferate within tumor environments. Bacterial structural and functional components can activate innate and adaptive immune responses, creating tumor-suppressive conditions that reduce tumor mass. Additionally, bacteria can deliver effector molecules directly into tumor cells, inducing apoptotic and necrotic cell death. Despite their potential, the use of bacteria in cancer immunotherapy poses risks due to possible toxicities and unpredictable in vivo behavior. Advances in genetic engineering have addressed these concerns by enabling the development of attenuated bacterial strains with enhanced anticancer properties for safer medical applications. This review highlights the role of bacteria in TME modulation, recent strategies to bioengineer bacterial pathogens as therapeutic tools, and the synergistic effects of combining bacteria with other immunotherapies. It also discusses the challenges and prospects of translating this innovative approach into clinical practice, offering a comprehensive overview of bacteria-based cancer immunotherapy's potential to reshape the future of cancer treatment.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"57 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989781","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

Characterisation of the ocular inflammatory response to AAV reveals divergence by sex and age. 对AAV的眼部炎症反应的特征显示出性别和年龄的差异。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-01-17 DOI: 10.1016/j.ymthe.2025.01.028

Alison J Clare,Philip M Langer,Amy Ward,Ying Kai Chan,Andrew D Dick,David A Copland

{"title":"Characterisation of the ocular inflammatory response to AAV reveals divergence by sex and age.","authors":"Alison J Clare,Philip M Langer,Amy Ward,Ying Kai Chan,Andrew D Dick,David A Copland","doi":"10.1016/j.ymthe.2025.01.028","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.01.028","url":null,"abstract":"Progress for ocular AAV gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry and bulk-sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes. Young males and females exhibited a similar dynamic response, with peak inflammation evident at D10-12 and signs of clinical resolution by D28. However, the magnitude of the transcriptional response by microglia and adaptive T cell infiltrate differed between sexes. With age, increased and persistent inflammation were observed in both sexes, though old males maintained their microglia transcriptional AAV response signature. Contrary, females demonstrated greater divergence in their inflammatory response across age, with enriched cellular stress and inflammatory gene expression in older mice, and corresponding signs of retinal degeneration. These findings inform crucial sex and age differences for therapeutic application of ocular gene therapy, highlighting the need to further understand these factors to overcome AAV immunogenicity.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"56 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989777","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