Human gene therapy最新文献_第2页

Vertex, Enlaza Launch Up-to-$2B Collaboration to Improve CASGEVY® Conditioning. Vertex与Enlaza达成高达20亿美元的合作，以改善CASGEVY®调理。

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-16 DOI: 10.1177/10430342251382168

Alex Philippidis

引用次数: 0

Lentiviral Gene Delivery Rescues Ciliary Defects in Patient-Derived Airway Organoids from Primary Ciliary Dyskinesia. 慢病毒基因递送拯救原发性纤毛运动障碍患者源性气道类器官的纤毛缺陷。

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-15 DOI: 10.1177/10430342251378128

Chunxiao Huo, Ting Luo, Lei Wu, Feng Yang, Zhangqi Xu, Xiaofen Tao, Junhua Xia, Tianhua Zhou, Yuan Jiang, Shanshan Xie

引用次数: 0

Preclinical Assessment of Antibody Responses to Adeno-Associated Virus (AAV) Vector-Based Capsids of AAV2, AAV5, AAV8, or AAV9 in Laboratory Cynomolgus Macaques (Macaca fascicularis) of Asian or Mauritian Origin. 亚洲或毛里求斯实验室食蟹猴（Macaca fascularis）对腺相关病毒（AAV）载体衣壳AAV2、AAV5、AAV8或AAV9抗体反应的临床前评估

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-12 DOI: 10.1177/10430342251376043

Betina Pajaziti, Ulf Michgehl, Dragica Blazevic, Franziska Fimm-Todt, Alexandra Duetting, Birgit Korbmacher, Stephanie Grote-Wessels, Stefan Michelfelder, Lars Mecklenburg

{"title":"Preclinical Assessment of Antibody Responses to Adeno-Associated Virus (AAV) Vector-Based Capsids of AAV2, AAV5, AAV8, or AAV9 in Laboratory Cynomolgus Macaques (Macaca fascicularis) of Asian or Mauritian Origin.","authors":"Betina Pajaziti, Ulf Michgehl, Dragica Blazevic, Franziska Fimm-Todt, Alexandra Duetting, Birgit Korbmacher, Stephanie Grote-Wessels, Stefan Michelfelder, Lars Mecklenburg","doi":"10.1177/10430342251376043","DOIUrl":"10.1177/10430342251376043","url":null,"abstract":"Adeno-associated virus (AAV)-based vectors are the most commonly used vectors for gene therapy. Wild-type AAV infections occur widely in humans and nonhuman primates (NHPs), and an accurate assessment of preexisting AAV antibodies is crucial for the efficient use of AAV-based gene therapies in preclinical and clinical studies. Cynomolgus macaques (Macaca fascicularis) are well-established preclinical large animal models for evaluating the efficacy and safety of AAV-mediated gene therapies intended for human use. We provide a retrospective evaluation comparing preexisting AAV-neutralizing or total antibody titers against serotypes AAV2, AAV5, AAV8, or AAV9 in cynomolgus macaque cohorts of Asian or Mauritian origin. We used an in vitro neutralizing antibody (NAB) assay to detect NAB titers or an in vitro Meso Scale Discovery-based assay for the quantification of total binding antibodies (TABs) in blood samples. Results were obtained to measure the serostatus of animals. In our analysis, the in vitro NAB assay revealed the lowest seroprevalence for AAV5 (13 ± 15% to 21 ± 6%) independent of origin. In the same assay, Asian animals were highly seropositive against AAV8, followed by AAV2 and AAV9 serotypes (88 ± 13%, 71 ± 10%, 69 ± 9%, respectively). Whereby, the prevalence of seropositivity was lower in animals of Mauritian origin with the highest seroprevalence for AAV9 (58 ± 7%), followed by AAV8 (53 ± 17%) and AAV2 (51 ± 20%) assessed by in vitro TAB assay. Notably, co-prevalences of antibody responses against AAV2, AAV8, and AAV9 serotypes resulted in 39.8% seropositivity (in vitro NAB assay) in NHPs of Asian and in about 32.6% (in vitro TAB assay) of Mauritian origin.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Safe and Efficacious Permanent Removal of Large COL7A1 Exons for Gene Reframing as a Reliable Therapeutic Strategy for Recessive Dystrophic Epidermolysis Bullosa. 安全有效的永久去除大COL7A1外显子进行基因重构是治疗隐性营养不良大疱性表皮松解症的可靠方法。

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-01 Epub Date: 2025-05-28 DOI: 10.1089/hum.2024.238

Sergio López-Manzaneda, Ángeles Mencía, José Bonafont, Alex Bassons-Bascuñana, Marta García, Alexander Nyström, Blanca Duarte, Sara Llames, Rodolfo Murillas, Silvia Modamio-Hoybjor, Matías Morín, Lucía Soletto, María J Escamez, Miguel A Moreno-Pelayo, Marcela Del Rio, Fernando Larcher

{"title":"Safe and Efficacious Permanent Removal of Large COL7A1 Exons for Gene Reframing as a Reliable Therapeutic Strategy for Recessive Dystrophic Epidermolysis Bullosa.","authors":"Sergio López-Manzaneda, Ángeles Mencía, José Bonafont, Alex Bassons-Bascuñana, Marta García, Alexander Nyström, Blanca Duarte, Sara Llames, Rodolfo Murillas, Silvia Modamio-Hoybjor, Matías Morín, Lucía Soletto, María J Escamez, Miguel A Moreno-Pelayo, Marcela Del Rio, Fernando Larcher","doi":"10.1089/hum.2024.238","DOIUrl":"10.1089/hum.2024.238","url":null,"abstract":"Mutations leading to premature termination codons in COL7A1 are commonly associated with severe generalized recessive dystrophic epidermolysis bullosa (RDEB). Previous research, including our own, has indicated that removing mutated COL7A1 exons along with the consequent reframing of COL7A1 may not pose noticeable impact on protein function, offering a potential therapeutic strategy. However, investigations into the long-term in vivo effects of genome editing-mediated removal of mutant exons have only focused on the small exon 80 thus far. Hence, this study focuses on exons 73 and 105 of COL7A1 to explore whether targeted exon removal, through a CRISPR/Cas9-assisted, Non-homologous end joining (NHEJ)-mediated approach, could be extended to other larger exons. Introducing ribonucleoprotein complexes carrying Cas9 and optimized sgRNA guide pairs for each exon (73 and 105) through electroporation efficiently led to their removal, consequently restoring type VII collagen (C7) synthesis in RDEB primary patient cells carrying frameshift mutations in these exons. In vitro tests indicated the normal stability of the resulting C7 variants expressed at physiological levels, while in vivo analyses of regenerated skin grafted onto immunodeficient mice using E73 or E105 RDEB edited cells demonstrated the proper deposition of C7 at the basement membrane zone, thereby restoring normal dermo-epidermal adherence. This study enhances the broader potential of the exon deletion approach in the treatment of RDEB.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"1211-1221"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Targeting Amyotrophic Lateral Sclerosis with Gene Therapy: From Silencing Genes to Enhancing Neuroprotection. 针对肌萎缩侧索硬化症的基因治疗：从沉默基因到增强神经保护。

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-01 Epub Date: 2025-09-04 DOI: 10.1177/10430342251372898

Sergi Verdés, Xavier Navarro, Assumpció Bosch

{"title":"Targeting Amyotrophic Lateral Sclerosis with Gene Therapy: From Silencing Genes to Enhancing Neuroprotection.","authors":"Sergi Verdés, Xavier Navarro, Assumpció Bosch","doi":"10.1177/10430342251372898","DOIUrl":"10.1177/10430342251372898","url":null,"abstract":"Gene therapy is emerging as a transformative approach for treating amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disease. While gene replacement has shown a groundbreaking success in spinal muscular atrophy, the complexity of ALS-due to frequent gain-of-function mutations and a heterogeneous etiology-presents significant challenges. Importantly, approximately 90% of ALS cases are sporadic, with unknown genetic mutation, further complicating patient stratification and therapeutic targeting. As a result, gene therapy strategies must often address multiple pathological mechanisms simultaneously. So far, current gene therapy strategies aim to either suppress toxic gene expression or promote neuroprotection, predominantly via viral-mediated delivery systems. This review will provide an overview of emerging preclinical and clinical gene therapy approaches for ALS, focusing on two main strategies: gene silencing and neuroprotection. Gene silencing techniques, including antisense oligonucleotides (ASOs), viral-mediated RNA interference, and gene editing, have demonstrated efficacy in reducing mutant gene expression, particularly in SOD1 and C9orf72 models, although clinical translation has so far yielded limited success. The recent Food and Drug Administration's approval of the ASO therapy Qalsody for SOD1-ALS underscores the clinical potential of these approaches. Neuroprotective strategies aim to enhance motor neuron survival through delivery of trophic factors, often targeting both central and peripheral tissues to harness retrograde transport mechanisms. We will discuss the advantages and limitations of various delivery vectors, targeting specificity, timing of intervention, and translational challenges, alongside current clinical trial data. This review aims to synthesize how these approaches may converge to address the multifaceted nature of ALS and guide the development of next-generation therapeutics.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"1173-1198"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

FDA Investigating Sarepta's Elevidys® after Second Patient Dies. 第二例患者死亡后FDA调查Sarepta的Elevidys®

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-01 Epub Date: 2025-08-04 DOI: 10.1177/10430342251366176

Alex Philippidis

引用次数: 0

Meta-Analysis and Optimization of the In Vitro Immortalization Assay for Safety Assessment of Retroviral Vectors in Gene Therapy. 逆转录病毒载体在基因治疗中安全性评估的体外永生化试验的meta分析和优化。

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-01 Epub Date: 2025-04-09 DOI: 10.1089/hum.2024.221

Antonella L Bastone, Philipp John-Neek, Violetta Dziadek, Friederike Mansel, Maike Hagedorn, Jenni Fleischauer, Bettina Weigel, Gabi Paul, Axel Schambach, Michael Rothe

引用次数: 0

Autologous Production: The Future of Sustainable Antibody Treatments. 自体生产：可持续抗体治疗的未来。

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-01 Epub Date: 2025-06-30 DOI: 10.1089/hum.2025.052

Steevens Bouaziz, Florence Rouleux-Bonnin, Stéphanie David, Guillermo Carvajal Alegria, Florence Velge-Roussel

{"title":"Autologous Production: The Future of Sustainable Antibody Treatments.","authors":"Steevens Bouaziz, Florence Rouleux-Bonnin, Stéphanie David, Guillermo Carvajal Alegria, Florence Velge-Roussel","doi":"10.1089/hum.2025.052","DOIUrl":"10.1089/hum.2025.052","url":null,"abstract":"Antibody gene transfer offers a promising solution to the high cost and frequent administration of monoclonal antibodies (mAbs), enabling the body to produce its own drugs economically and sustainably. This review addresses the challenges faced by antibody therapies, including economic and environmental impacts, as well as patient-related issues such as efficacy and tolerance. We propose that direct in vivo protein production, or autologous production, via plasmid DNA (pDNA) injection may address some of these challenges. This pDNA-based strategy provides a cost-effective alternative while maintaining flexibility and adaptability for various proteins, making it suitable for a wide range of pathological contexts. Additionally, gene therapy with plasmids could reduce the need for frequent injections, improving patient compliance. In this review, we provide an overview of the pioneering studies that introduced the use of pDNA for in vivo protein production. We focus on key factors for successful autologous production, such as plasmid design, vectorization, and methods of administration. Finally, we explore various applications where autologous production could serve as a promising alternative for therapeutic antibody treatments.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"1222-1236"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Advancements in Nonviral Gene Editing Strategies for Rare Diseases. 罕见病非病毒基因编辑策略研究进展

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-01 DOI: 10.1177/10430342251372056

Jimena Pérez-Maroto, Laura Sepp-Lorenzino, Diego Castaño-Esteban, Daniela Palacios, Begoña Sot

{"title":"Advancements in Nonviral Gene Editing Strategies for Rare Diseases.","authors":"Jimena Pérez-Maroto, Laura Sepp-Lorenzino, Diego Castaño-Esteban, Daniela Palacios, Begoña Sot","doi":"10.1177/10430342251372056","DOIUrl":"10.1177/10430342251372056","url":null,"abstract":"Rare diseases are serious and often chronic conditions that affect a small number of individuals. However, with over 7,000 rare diseases identified, their cumulative global numbers and impact are substantial. A considerable proportion of these conditions is caused by genetic abnormalities. Among these, monogenic disorders are of particular relevance, as they are caused by mutations in specific genes. The development of gene therapy, and more specifically, gene editing, offers innovative approaches to treat these rare diseases. A significant challenge associated with the implementation of such strategies concerns the delivery of gene editing tools. Nonviral vectors based on nanomaterials have demonstrated considerable potential as promising alternatives to viral vectors, thereby overcoming their disadvantages. The biocompatibility and tunability of nanoparticles, along with their potential capacity to target diverse tissues, positions them as a promising therapeutic approach for the treatment of a wide range of organ-specific rare diseases. Here, we review current progress in the development and evaluation of novel nanomedicine strategies for gene editing in rare diseases, highlighting new gene editing approaches, delivery systems, and potential targets.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"1118-1137"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Hospital Exemption for Advanced Therapy Medicinal Products in Spain. 西班牙高级治疗药品的医院豁免。

IF 4 3区医学

Human gene therapy Pub Date : 2025-09-01 Epub Date: 2025-08-22 DOI: 10.1177/10430342251372050

Marcos Timón, Sol Ruiz

引用次数: 0