Molecular Therapy最新文献_第10页

Gene therapy then and now: A look back at changes in the field over the past 25 years. 基因治疗的过去与现在：回顾过去 25 年该领域的变化。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-02-28 DOI: 10.1016/j.ymthe.2025.02.040

Dan Wang, Gregg Stevens, Terence R Flotte

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Redefining quality in cell and gene therapies: Lessons from implementing electronic QMS in academic cGMP facility. 重新定义细胞和基因治疗的质量：在学术cGMP设施中实施电子质量管理体系的经验教训。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-03-31 DOI: 10.1016/j.ymthe.2025.03.050

Xia Wu, Amaia Cadinanos-Garai, Vivian Quach, Eric Jurado, Alix Vaissié, Mohamed Abou-El-Enein

{"title":"Redefining quality in cell and gene therapies: Lessons from implementing electronic QMS in academic cGMP facility.","authors":"Xia Wu, Amaia Cadinanos-Garai, Vivian Quach, Eric Jurado, Alix Vaissié, Mohamed Abou-El-Enein","doi":"10.1016/j.ymthe.2025.03.050","DOIUrl":"10.1016/j.ymthe.2025.03.050","url":null,"abstract":"Manufacturing cell and gene therapies (CGTs) involves complex processes that require robust quality management, especially within academic current Good Manufacturing Practice (cGMP) facilities, where resources are often limited. Traditional paper-based quality management systems (QMSs), while initially convenient, often become burdensome, leading to errors, poor traceability, and compliance risks. Electronic QMSs (eQMSs) are gaining recognition for their ability to centralize and automate key quality processes, significantly enhancing operational efficiency and regulatory readiness. Through an in-depth case study of the University of Southern California and Children's Hospital of Los Angeles academic cGMP facility, this review demonstrates tangible improvements achieved by adopting an eQMS. Practical insights gained from this experience are shared, including careful selection of eQMS platforms, phased rollout strategies, and comprehensive staff training. The review also addresses common implementation challenges and suggests practical solutions to overcome them. Lessons learned and strategies discussed here can serve as valuable guidance for other academic institutions considering eQMS adoption. Ultimately, embracing an eQMS enables academic CGT manufacturers to operate more efficiently and stay ahead in a fast-moving field.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2091-2103"},"PeriodicalIF":12.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy. 用于基因治疗的造血干细胞和祖细胞的体外修饰。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-04-01 DOI: 10.1016/j.ymthe.2025.03.058

David A Williams, Donald B Kohn, Adrian J Thrasher

{"title":"Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy.","authors":"David A Williams, Donald B Kohn, Adrian J Thrasher","doi":"10.1016/j.ymthe.2025.03.058","DOIUrl":"10.1016/j.ymthe.2025.03.058","url":null,"abstract":"The development of viral vectors has been particularly critical for genetic therapies of hematological diseases. Before the development of retrovirus vectors (RVVs), gene transfer into mammalian cells was accomplished by transduction of DNA plasmids by chemical means and later by electroporation. The main limitation of these methods is the inefficiency of transfer of intact sequences, and particularly with electroporation significant cell death of the manipulated cells. The earliest successful human gene therapy trials utilized γ-RVVs and many of the techniques developed in the 1980s. A breakthrough for the field was the exploitation and development of HIV for transfer vectors, termed lentivirus vectors. In this review, we highlight uses of retro- and lentivirus vectors in monogenic diseases in which hematopoietic stem cells are used in the autologous setting to treat immunodeficiencies, hemoglobinopathies and metabolic diseases. The three authors' perspective represent experiences in the field over four decades that encompasses both basic translational research and development and oversight of early and ongoing gene therapy trials utilizing viral vectors.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2141-2153"},"PeriodicalIF":12.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Recent progress and future challenges in structure-based protein-protein interaction prediction. 基于结构的蛋白-蛋白相互作用预测的最新进展和未来挑战。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-04-06 DOI: 10.1016/j.ymthe.2025.04.003

Rongqing Yuan, Jing Zhang, Jian Zhou, Qian Cong

引用次数: 0

The past, present, and future of RNA vaccines. RNA疫苗的过去、现在和未来。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-02-19 DOI: 10.1016/j.ymthe.2025.02.016

John S Tregoning, Niek N Sanders

引用次数: 0

ABI and generative biology: A new paradigm for gene therapy, genome engineering, and engineered cell therapy. ABI 和生成生物学：基因治疗、基因组工程和工程细胞疗法的新范例。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-03-21 DOI: 10.1016/j.ymthe.2025.02.021

Adrian Woolfson

引用次数: 0

The curious case of AAV immunology. AAV免疫学的奇特案例。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-03-27 DOI: 10.1016/j.ymthe.2025.03.037

Allison M Keeler, Wei Zhan, Sanjay Ram, Katherine A Fitzgerald, Guangping Gao

{"title":"The curious case of AAV immunology.","authors":"Allison M Keeler, Wei Zhan, Sanjay Ram, Katherine A Fitzgerald, Guangping Gao","doi":"10.1016/j.ymthe.2025.03.037","DOIUrl":"10.1016/j.ymthe.2025.03.037","url":null,"abstract":"Immune responses to adeno-associated virus (AAV) have long been perplexing, from its first discovery to the latest clinical trials of recombinant AAV (rAAV) therapy. Wild-type AAV (wtAAV) does not cause any known disease, making it an ideal vector for gene therapy, as viral vectors retain virus-like properties. Although AAV stimulates only a mild immune response compared with other viruses, it is still recognized by the innate immune system and induces adaptive immune responses. B cell responses against both wtAAV and rAAV are robust and can hinder gene therapy applications and prevent redosing. T cell responses can clear transduced cells or establish tolerance against gene therapy. Immune responses to AAV gene therapy are influenced by many factors. Most clinical immunotoxicities that develop in response to gene therapies have emerged as higher doses of AAV vectors have been utilized and were not properly modeled in preclinical animal studies. Thus, several strategies have been undertaken to reduce or mitigate immune responses to AAV. While we have learned a considerable amount about how the immune system responds to AAV gene therapy since the discovery of AAV virus, it still remains a curious case that requires more investigation to fully understand.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"1946-1965"},"PeriodicalIF":12.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Four decades of adenovirus gene transfer vectors: History and current use. 腺病毒基因转移载体的四十年：历史和当前使用情况。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-04-02 DOI: 10.1016/j.ymthe.2025.03.062

Neil R Hackett, Ronald G Crystal

{"title":"Four decades of adenovirus gene transfer vectors: History and current use.","authors":"Neil R Hackett, Ronald G Crystal","doi":"10.1016/j.ymthe.2025.03.062","DOIUrl":"10.1016/j.ymthe.2025.03.062","url":null,"abstract":"Replication-deficient adenovirus-based gene therapy vectors were the first vectors demonstrated to mediate effective, robust in vivo gene transfer. The ease of genome engineering, large carrying capacity, and methods for large-scale vector production made adenoviral vectors a primary focus in the early days of gene therapy. Many vector modifications such as capsid engineering and regulated and cell-specific transgene expression were first demonstrated in adenovirus (Ad) vectors. However, early human studies proved disappointing, with safety and efficacy issues arising from anti-vector innate and acquired immune responses. While many gene therapy researchers moved to other vectors, others recognized that the immune response and limited duration of transgene expression were useful in the correct context. The striking example of this was the use of several effective adenovirus vectors engineered as COVID-19 vaccines estimated to have been administered to 2 billion people. In addition to vaccines, current applications of Ad vectors relate to anti-cancer therapies, tissue remodeling, and gene editing.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2192-2204"},"PeriodicalIF":12.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Gene regulation technologies for gene and cell therapy. 基因和细胞治疗中的基因调控技术。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-04-06 DOI: 10.1016/j.ymthe.2025.04.004

Gabriel L Butterfield, Samuel J Reisman, Nahid Iglesias, Charles A Gersbach

{"title":"Gene regulation technologies for gene and cell therapy.","authors":"Gabriel L Butterfield, Samuel J Reisman, Nahid Iglesias, Charles A Gersbach","doi":"10.1016/j.ymthe.2025.04.004","DOIUrl":"10.1016/j.ymthe.2025.04.004","url":null,"abstract":"Gene therapy stands at the forefront of medical innovation, offering unique potential to treat the underlying causes of genetic disorders and broadly enable regenerative medicine. However, unregulated production of therapeutic genes can lead to decreased clinical utility due to various complications. Thus, many technologies for controlled gene expression are under development, including regulated transgenes, modulation of endogenous genes to leverage native biological regulation, mapping and repurposing of transcriptional regulatory networks, and engineered systems that dynamically react to cell state changes. Transformative therapies enabled by advances in tissue-specific promoters, inducible systems, and targeted delivery have already entered clinical testing and demonstrated significantly improved specificity and efficacy. This review highlights next-generation technologies under development to expand the reach of gene therapies by enabling precise modulation of gene expression. These technologies, including epigenome editing, antisense oligonucleotides, RNA editing, transcription factor-mediated reprogramming, and synthetic genetic circuits, have the potential to provide powerful control over cellular functions. Despite these remarkable achievements, challenges remain in optimizing delivery, minimizing off-target effects, and addressing regulatory hurdles. However, the ongoing integration of biological insights with engineering innovations promises to expand the potential for gene therapy, offering hope for treating not only rare genetic disorders but also complex multifactorial diseases.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2104-2122"},"PeriodicalIF":12.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A synthetic opsin restores vision in patients with severe retinal degeneration. 一种人工合成的视蛋白能恢复严重视网膜变性患者的视力。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-05-07 Epub Date: 2025-03-21 DOI: 10.1016/j.ymthe.2025.03.031

Samarendra K Mohanty, Santosh Mahapatra, Subrata Batabyal, Michael Carlson, Gayatri Kanungo, Ananta Ayyagari, Kissaou Tchedre, Joel A Franco, Michael Singer, Samuel B Barone, Sai Chavala, Vinit B Mahajan

{"title":"A synthetic opsin restores vision in patients with severe retinal degeneration.","authors":"Samarendra K Mohanty, Santosh Mahapatra, Subrata Batabyal, Michael Carlson, Gayatri Kanungo, Ananta Ayyagari, Kissaou Tchedre, Joel A Franco, Michael Singer, Samuel B Barone, Sai Chavala, Vinit B Mahajan","doi":"10.1016/j.ymthe.2025.03.031","DOIUrl":"10.1016/j.ymthe.2025.03.031","url":null,"abstract":"Inherited retinal degenerations are the leading cause of blindness worldwide, and, in advanced stages, cell loss makes gene replacement ineffective. Optogenetics offers a therapeutic opportunity to restore vision by photo-sensitizing remaining retinal neurons. However, current opsins are kinetically slow, partially activated in ambient light, unresponsive to different light colors, and target low-resolution retinal cell circuits. To overcome these limits, we engineered a synthopsin made of three selectively mutated non-mammalian proteins to achieve a broadband multi-characteristic opsin. The synthopsin was packaged into an optimized AAV2 gene-therapy vector that targets human retinal bipolar cells. In an investigator-initiated, open-label study, four blind retinitis pigmentosa patients with ABCA4 variants received a single intravitreal gene-therapy injection. Noninvasive imaging confirmed retinal gene expression via a fluorescent reporter protein. Patients showed improvement in vision, shape discrimination, and mobility through 52 weeks. There were no significant safety issues despite what is likely one of the most synthetic, non-mammalian proteins ever expressed in a human. This is the first report of a gene monotherapy that can restore vision in blind patients in a mutation-independent manner utilizing an optogenetics technology platform.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"2279-2290"},"PeriodicalIF":12.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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