Molecular TherapyPub Date : 2025-06-21DOI: 10.1016/j.ymthe.2025.06.002
Valentino Bezzerri, Marco Cipolli
{"title":"Beyond the bench: Revitalizing ataluren development for rare genetic disorders","authors":"Valentino Bezzerri, Marco Cipolli","doi":"10.1016/j.ymthe.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.002","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"70 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337554","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}
Molecular TherapyPub Date : 2025-06-21DOI: 10.1016/j.ymthe.2025.06.007
Hanadi Saliba, David Alexandre Gross, Giuseppe Ronzitti
{"title":"Harnessing B19-directed CAR T cells for AAV vector administration in seropositive patients: The importance of the niche","authors":"Hanadi Saliba, David Alexandre Gross, Giuseppe Ronzitti","doi":"10.1016/j.ymthe.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.007","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"47 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337556","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}
Molecular TherapyPub Date : 2025-06-21DOI: 10.1016/j.ymthe.2025.06.015
Glenn Yiu
{"title":"Bispecific receptor decoys: A new player to a crowded field","authors":"Glenn Yiu","doi":"10.1016/j.ymthe.2025.06.015","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.015","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"3 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337558","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}
{"title":"Effective Use of BCMA-Targeting Bispecific T-Cell-Engaging Antibody in Treatment Refractory LRP4-positive Myasthenia Gravis.","authors":"Stefanie Schreiber,Marwa Al-Dubai,Stefan Vielhaber,Lora Lefterova,Sascha Dietrich,Tobias Ruck,Sven Meuth,Denise Walther,Dimitrios Mougiakakos","doi":"10.1016/j.ymthe.2025.06.029","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.029","url":null,"abstract":"Myasthenia gravis (MG) is an antibody-mediated autoimmune disease affecting the neuromuscular junction. Refractory MG, particularly in cases associated with rare anti-LRP4 antibodies, presents significant treatment challenges. Teclistamab, a bispecific antibody targeting BCMA and CD3, redirects T cells against plasma cells and is approved for multiple myeloma treatment. Increasing interest surrounds the use of T-cell-based therapies in B-cell-mediated autoimmune diseases, particularly CAR T cells, which have demonstrated efficacy in achieving deep B-cell depletion and durable remissions. Additionally, emerging data support the use of T cell engagers (TCEs) as an alternative strategy for targeting autoreactive B cells. We report the case of a 47-year-old woman with severe, refractory, LRP4-positive MG. Despite multiple treatments, she remained severely affected, wheelchair-bound, and experiencing significant disability. Off-label teclistamab administration resulted in mild cytokine release syndrome (CRS), self-resolving lymphopenia, and hypogammaglobulinemia. Residual circulating B cells were eliminated, anti-LRP4 antibodies became undetectable, and clinical scores improved significantly. The patient regained mobility and has sustained remission during short-term follow-up. This case highlights the therapeutic potential of teclistamab and BCMA-targeting strategies in MG, warranting further investigation.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"44 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320095","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}
Molecular TherapyPub Date : 2025-06-17DOI: 10.1016/j.ymthe.2025.06.021
Lucia Nicosia,Patrick T Harrison
{"title":"CRISPR for Cystic Fibrosis: advances and insights from a systematic review.","authors":"Lucia Nicosia,Patrick T Harrison","doi":"10.1016/j.ymthe.2025.06.021","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.06.021","url":null,"abstract":"Cystic Fibrosis (CF) is a severe genetic disorder caused by loss-of-function mutations in the CFTR gene. Gene editing approaches have the potential to correct such mutations. This systematic review outlines the mechanisms of the main CRISPR-based technologies, and, through cross-study comparisons, analyzes twenty-seven research articles that applied these technologies to target CF-causing variants. We report and discuss the strategy design, target cell selection, editing efficiency, prevalence of editing byproducts and levels of CFTR functional restoration achieved in each work, with the aim of providing technical insights for further exploration of CRISPR-based gene editing approaches. Our findings show that the F508del and W1282X mutations were the most extensively studied CF-causing variants, though over fifteen mutations were targeted overall. The majority of works under review explored the use of homology-directed repair (HDR) or base editing, with a growing number reporting efficient prime editing. Some studies tackled multiple individual mutations, compared different editors, or tested strategies across various models, while others focused on approaches that rescue CFTR function without directly correcting a mutation. Several works also proposed strategies that could address multiple variants with a single approach, while others highlighted technical difficulties in editing certain regions of the CFTR gene. This cross-study comparison also emphasizes the need for standardized reporting of editing efficiency and functional rescue, and stresses the importance of further single-cell RNA sequencing and in-vivo studies to reach clinically-relevant conclusions. However, as gene editing techniques continue to evolve, and with over sixty ongoing CRISPR-based clinical trials, there is growing optimism for meaningful advancements in CF gene-editing therapeutics.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"89 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320097","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}