Molecular Therapy-Methods & Clinical Development最新文献

Why regulatory T cells love lactic acid. 为什么调节性T细胞喜欢乳酸。

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-29 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101647

Avik Chattopadhyay, Leonardo M R Ferreira

引用次数: 0

When pullulanase needs a little push: MyoAAV capsids enhance gene therapy for GSD IIIa. 当普鲁兰酶需要一点推动时：MyoAAV衣壳增强GSD IIIa的基因治疗。

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-29 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101648

Sree Venigalla, Christina A Pacak

引用次数: 0

Rapid kinetics of AAV8 delivery of Vglut3 and hearing rescue shown day-by-day via matched IHC and ABR. 通过匹配的IHC和ABR显示AAV8递送Vglut3和听力拯救的快速动力学。

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-27 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101638

Cole W D Peters, Killian Hanlon

引用次数: 0

Toward CAR-B cells for HIV-1 therapy. CAR-B细胞用于HIV-1治疗

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-26 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101639

Yiming Yin, Michael Farzan

引用次数: 0

The Advanced Therapies model of Lund an integrated approach to accelerate access for many patients. 隆德的先进疗法模式是一种加速许多患者获得治疗的综合方法。

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-25 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101637

Gisela Helenius, Stefan Jovinge, Anna Falk

{"title":"The Advanced Therapies model of Lund an integrated approach to accelerate access for many patients.","authors":"Gisela Helenius, Stefan Jovinge, Anna Falk","doi":"10.1016/j.omtm.2025.101637","DOIUrl":"10.1016/j.omtm.2025.101637","url":null,"abstract":"Scientific breakthroughs in the field of cell and gene therapy lay the groundwork for therapeutic innovation, but their translation and integration into routine care is delayed by systemic inefficiencies and limited cross-sector alignment. The Advanced Therapies model of Lund is a proactive and integrated approach designed to accelerate the development of advanced therapies from discovery to reimbursement, facilitating close collaboration among three main entities: university, hospital, and the iActors (a coalition of the innovation system, incubators, investors, and industry). Unlocking the full potential of therapeutic innovation requires inclusive and proactive engagement from all entities to accelerate development timelines, optimize resource use across the ecosystem, and ultimately deliver curative, cost-effective advanced therapies to patients. This will ensure broad patient access and establishment of optimal conditions for developing the next generation of cell and gene therapies, while also facilitating innovation and economic growth. To operationalize this model, we developed the Cell and Gene Therapy Navigator, a visualization instrument designed to track and optimize the development of advanced therapies within the model framework. This tool leverages three-dimensional visualization to provide a dynamic and comprehensive overview of progress of the advanced therapy development across the three crucial entities: university, hospital, and iActors. We are confident that working according to the model will minimize translational gaps and result in seamless good manufacturing practices (GMP) transfer, fewer re-works, faster time to first-in-human, and the creation of more viable biotech companies.","PeriodicalId":54333,"journal":{"name":"Molecular Therapy-Methods & Clinical Development","volume":"33 4","pages":"101637"},"PeriodicalIF":4.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12688660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erratum: Genome Editing in Patient iPSCs Corrects the Most Prevalent USH2A Mutations and Reveals Intriguing Mutant mRNA Expression Profiles. 勘误：患者iPSCs中的基因组编辑纠正了最普遍的USH2A突变并揭示了有趣的突变mRNA表达谱。

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-24 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101645

Carla Sanjurjo-Soriano, Nejla Erkilic, David Baux, Daria Mamaeva, Christian P Hamel, Isabelle Meunier, Anne-Françoise Roux, Vasiliki Kalatzis

引用次数: 0

AAV-mediated gene therapy for the CNS: The case for early treatment. aav介导的中枢神经系统基因治疗：早期治疗的案例。

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-24 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101640

Luanna E Liebscher Vidal, Jose M Martinez-Navio

引用次数: 0

Tailoring monocyte-derived tolerogenic cell therapies to the needs; what's in a name? 根据需要定制单核细胞衍生的耐受性细胞疗法；名字里有什么？

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-21 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101634

Tatjana Nikolic, Bart O Roep

引用次数: 0

HBVZ10, an AAV8 vector-based new HBV therapy candidate for cccDNA elimination. HBVZ10，一种基于AAV8载体的新型HBV治疗候选物，用于消除cccDNA。

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-19 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101646

Bai-Hua Zhang, Yuanping Zhou, Stephen Horrigan, Laura Luckenbaugh, Jianming Hu, Fabien Zoulim, Yong-Yuan Zhang

{"title":"HBVZ10, an AAV8 vector-based new HBV therapy candidate for cccDNA elimination.","authors":"Bai-Hua Zhang, Yuanping Zhou, Stephen Horrigan, Laura Luckenbaugh, Jianming Hu, Fabien Zoulim, Yong-Yuan Zhang","doi":"10.1016/j.omtm.2025.101646","DOIUrl":"10.1016/j.omtm.2025.101646","url":null,"abstract":"Eliminating hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) remains a major challenge, requiring innovative treatment strategies and drug candidates. Clinical studies reveal that wild-type HBV in the blood is often replaced by gradually rising mutant populations. This replacement reflects loss of the early cccDNA pool, then replenished predominantly through de novo infection. We proposed that blocking de novo infection is essential for cccDNA elimination and establishing a finite HBV treatment regimen. To achieve sustained inhibition of de novo cccDNA replenishment, we developed HBVZ10, a gene therapy candidate that utilizes an optimized adeno-associated virus (AAV) vector 8 to deliver human anti-HBs antibody genes into muscle cells for expanding endogenous anti-HBs antibody production capacity. HBVZ10 expression and therapeutic function were evaluated in uPA/SCID chimeric mice. HBVZ10 therapy achieved sustained antibody expression of ≥100,000 mIU/mL for at least 200 days following a single dose administration. Combining HBVZ10 with intracellular replication inhibitor entecavir resulted in >100-fold reductions in cccDNA within a few months, accompanied by progressive reductions in serum HBeAg and HBsAg to undetectable levels. These findings establish preclinical evidence of HBVZ10 as a novel gene therapy candidate and support a paradigm-shifting cccDNA elimination strategy.","PeriodicalId":54333,"journal":{"name":"Molecular Therapy-Methods & Clinical Development","volume":"33 4","pages":"101646"},"PeriodicalIF":4.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR/methotrexate-integrated strategy for TCR-T cell engineering with reduced chromosome 14 loss. 减少14号染色体丢失的TCR-T细胞工程CRISPR/甲氨蝶呤整合策略

IF 4.7 2区医学

Molecular Therapy-Methods & Clinical Development Pub Date : 2025-11-17 eCollection Date: 2025-12-11 DOI: 10.1016/j.omtm.2025.101635

Jian Xu, Lianghua Shen, Ziyu Chen, Changmeng Zhang, Xiaodan Ding, Qiaomei He, Xiao Zhou, Peiyao Jiang, Jiayu Liu, Lu Li, Jinan Fang, Fanlin Li, Liping Wan, Xueying Ding, Yuqin Yang, Xiaorui Wang, Pengran Wang, Xianmin Song, Yan Zhang

{"title":"CRISPR/methotrexate-integrated strategy for TCR-T cell engineering with reduced chromosome 14 loss.","authors":"Jian Xu, Lianghua Shen, Ziyu Chen, Changmeng Zhang, Xiaodan Ding, Qiaomei He, Xiao Zhou, Peiyao Jiang, Jiayu Liu, Lu Li, Jinan Fang, Fanlin Li, Liping Wan, Xueying Ding, Yuqin Yang, Xiaorui Wang, Pengran Wang, Xianmin Song, Yan Zhang","doi":"10.1016/j.omtm.2025.101635","DOIUrl":"10.1016/j.omtm.2025.101635","url":null,"abstract":"Adoptive T cell therapy, particularly T cell receptor-engineered T (TCR-T) cell therapy, holds promise for cancer treatment in solid tumors and hematological malignancies. Conventional lentiviral TCR-T cell therapies face insertional mutagenesis risks, while CRISPR-mediated T cell receptor α constant (TRAC) locus targeting suffers from suboptimal knockin efficiency and chromosome 14 loss. To address these challenges, we introduced a non-viral strategy combining CRISPR-Cas9 electroporation with methotrexate (MTX) metabolic selection. Primary human T cells were engineered to integrate a CMV-pp65-specific TCR and an MTX-resistant dihydrofolate reductase (DHFR)-FS cassette into the TRAC locus via homology-directed repair (HDR). Systematic optimization of electroporation timing, buffer systems, and HDR enhancers achieved initial TCR integration efficiency of ∼20%. Subsequent 6-day MTX treatment enriched engineered cells to ∼70% purity while selectively depleting unedited and chromosomally aberrant clones. Fluorescence in situ hybridization revealed that MTX enrichment reduced CRISPR-associated chromosome 14 loss comparable to unedited T cells. Functionally, TRAC-TCR-T cells exhibited enhanced interferon (IFN)-γ/tumor necrosis factor alpha (TNF-α) secretion and reduced exhaustion markers versus lentiviral counterparts, while maintaining equivalent tumor clearance efficacy in vitro and in xenograft models. In conclusion, this integrated platform mitigates viral vector risks, alleviates concerns of CRISPR-associated genomic instability, and provides a good manufacturing practice (GMP)-compatible approach that may facilitate the development of safer adoptive TCR-T immunotherapies.","PeriodicalId":54333,"journal":{"name":"Molecular Therapy-Methods & Clinical Development","volume":"33 4","pages":"101635"},"PeriodicalIF":4.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12686916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0