Human gene therapy最新文献_第6页

Call for Papers: Special Issue on Ocular Gene Therapy. 征稿启事：眼部基因治疗特刊。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 DOI: 10.1089/hum.2024.42267

引用次数: 0

Pfizer Marks Phase III Success in Hemophilia A, then Layoffs after Failure in DMD. 辉瑞在 A 型血友病 III 期治疗中取得成功，但在 DMD 治疗失败后裁员。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 DOI: 10.1089/hum.2024.378422.tlg

Alex Philippidis

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Intra-Articular Delivery of an AAV-Anti-TNF-α Vector Alleviates the Progress of Arthritis in a RA Mouse Model. 关节内输送 AAV 抗 TNF-α 载体可减轻关节炎小鼠模型的关节炎进展。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 Epub Date: 2024-08-12 DOI: 10.1089/hum.2024.084

Xiao Ke, Qing Xie, Shuang Luo, Qingwei Li, Qiang Zheng, Zhirong Zhang

{"title":"Intra-Articular Delivery of an AAV-Anti-TNF-α Vector Alleviates the Progress of Arthritis in a RA Mouse Model.","authors":"Xiao Ke, Qing Xie, Shuang Luo, Qingwei Li, Qiang Zheng, Zhirong Zhang","doi":"10.1089/hum.2024.084","DOIUrl":"10.1089/hum.2024.084","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease marked by joint destruction and functional impairment. Tumor necrosis factor (TNF) plays a critical role in RA pathogenesis. Although TNF-targeting drugs are clinically effective, their need for frequent and long-term administration often results in poor patient adherence and suboptimal outcomes. This study developed a gene therapy approach using engineered adeno-associated virus (AAV) vectors to deliver an anti-TNF agent directly into the joint cavity of RA animal models. Animals receiving this therapy demonstrated sustained improvement in clinical scores, inflammatory markers, and joint tissue health. Immunofluorescence staining revealed that AAV vectors could transduce various cell types, including T cells, type A synoviocytes, and dendritic cells. Our results indicate that a single administration of this gene therapy provided long-term efficacy. This suggests that AAV-mediated anti-TNF gene therapy can offer prolonged relief from clinical symptoms and reduce inflammatory damage in a mouse model of RA. This innovative approach presents a promising new therapy with significant clinical prospects to treat patients with RA.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"754-766"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751544","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}

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Introduction to ESGCT 2024 Special Issue. ESGCT 2024 特刊简介。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 DOI: 10.1089/hum.2024.35178

Alberto Auricchio

引用次数: 0

Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for Human Gene Therapy. 罗莎琳德-富兰克林学会自豪地宣布 2023 年人类基因疗法奖获得者。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 DOI: 10.1089/hgt.2024.32445.rfs2023

Gloria Gonzalez Aseguinolaza

引用次数: 0

Modulation of AAV9 Galactose Binding Yields Novel Gene Therapy Vectors and Predicts Cross-Species Differences in Glycan Avidity. 调节 AAV9 的半乳糖结合可产生新的基因治疗载体，并可预测糖酶活性的跨物种差异。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 Epub Date: 2024-08-13 DOI: 10.1089/hum.2024.050

Jacob A Hoffman, Nathan Denton, Joshua J Sims, Rosemary Meggersee, Zhe Zhang, Kanyin Olagbegi, James M Wilson

{"title":"Modulation of AAV9 Galactose Binding Yields Novel Gene Therapy Vectors and Predicts Cross-Species Differences in Glycan Avidity.","authors":"Jacob A Hoffman, Nathan Denton, Joshua J Sims, Rosemary Meggersee, Zhe Zhang, Kanyin Olagbegi, James M Wilson","doi":"10.1089/hum.2024.050","DOIUrl":"10.1089/hum.2024.050","url":null,"abstract":"Effective use of adeno-associated viruses (AAVs) for clinical gene therapy is limited by their propensity to accumulate in and transduce the liver. This natural liver tropism is associated with severe adverse events at the high doses that can be necessary for achieving therapeutic transgene expression in extrahepatic tissues. To improve the safety and cost of AAV gene therapy, capsid engineering efforts are underway to redirect in vivo AAV biodistribution away from the liver toward disease-relevant peripheral organs such as the heart. Building on previous work, we generated a series of AAV libraries containing variations at three residues (Y446, N470, and W503) of the galactose-binding pocket of the AAV9 VP1 protein. Screening of this library in mice identified the XRH family of variants (Y446X, N470R, and W503H), the strongest of which, HRH, exhibited a 6-fold reduction in liver RNA expression and a 10-fold increase in cardiac RNA expression compared with wild-type AAV9 in the mouse. Screening of our library in a nonhuman primate (NHP) revealed reduced performance of AAV9 and two closely related vectors in the NHP liver compared with the mouse liver. Measurement of the galactose-binding capacity of our library further identified those same three vectors as the only strong galactose binders, suggesting an altered galactose presentation between the mouse and NHP liver. N-glycan profiling of these tissues revealed a 9% decrease in exposed galactose in the NHP liver compared with the mouse liver. In this work, we identified a novel family of AAV variants with desirable biodistribution properties that may be suitable for targeting extrahepatic tissues such as the heart. These data also provide important insights regarding species- and tissue-specific differences in glycan presentation that may have implications for the development and translation of AAV gene therapies.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"734-753"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603567","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

Lipid Nanoparticles for Nucleic Acid Delivery Beyond the Liver. 用于在肝脏外输送核酸的脂质纳米颗粒。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 Epub Date: 2024-08-28 DOI: 10.1089/hum.2024.106

Nadine Saber, Mariona Estapé Senti, Raymond M Schiffelers

引用次数: 0

Advances in MicroRNA Therapeutics: From Preclinical to Clinical Studies. 微RNA疗法的进展：从临床前研究到临床研究。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 DOI: 10.1089/hum.2024.113

Simona Brillante, Mariagrazia Volpe, Alessia Indrieri

{"title":"Advances in MicroRNA Therapeutics: From Preclinical to Clinical Studies.","authors":"Simona Brillante, Mariagrazia Volpe, Alessia Indrieri","doi":"10.1089/hum.2024.113","DOIUrl":"10.1089/hum.2024.113","url":null,"abstract":"MicroRNAs (miRNAs) are crucial regulators of gene expression involved in various pathophysiological processes. Their ability to modulate multiple pathways simultaneously and their involvement in numerous diseases make miRNAs attractive tools and targets in therapeutic development. Significant efforts have been made to advance miRNA research in the preclinical stage, attracting considerable investment from biopharmaceutical companies. Consequently, an increasing number of miRNA-based therapies have entered clinical trials for both diagnostic and therapeutic applications across a wide range of diseases. While individual miRNAs can regulate a broad array of mRNA targets, this also complicates the management of adverse effects seen in clinical trials. Several candidates have been discontinued due to toxicity concerns, underscoring the need for comprehensive risk assessments of miRNA therapeutics. Despite no miRNA-based strategies have yet received approval from regulatory agencies, prominent progress in the miRNA modulation approaches and in the nano-delivery systems have been made in the last decade, leading to the development of novel safe and well-tolerated miRNA drug candidates. In this review, we present recent advances in the development of miRNA therapeutics currently in preclinical or clinical stages for treating both rare genetic disorders and multifactorial common conditions. We also address the challenges related to the safety and targeted delivery of miRNA therapies, as well as the identification of the most effective therapeutic candidates in preclinical and clinical trials.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"628-648"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987878","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

Call for Papers: Special Issue on Toxicity And Safety in Clinical AAV Gene Therapy. 征稿启事：临床 AAV 基因疗法的毒性和安全性特刊。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 DOI: 10.1089/hum.2024.85296

引用次数: 0

Insights into Prime Editing Technology: A Deep Dive into Fundamentals, Potentials, and Challenges. 深入了解基因编辑技术：深入探讨基本原理、潜力和挑战。

IF 3.9 3区医学

Human gene therapy Pub Date : 2024-09-01 Epub Date: 2024-07-01 DOI: 10.1089/hum.2024.043

Seyed Younes Hosseini, Rahul Mallick, Petri Mäkinen, Seppo Ylä-Herttuala

{"title":"Insights into Prime Editing Technology: A Deep Dive into Fundamentals, Potentials, and Challenges.","authors":"Seyed Younes Hosseini, Rahul Mallick, Petri Mäkinen, Seppo Ylä-Herttuala","doi":"10.1089/hum.2024.043","DOIUrl":"10.1089/hum.2024.043","url":null,"abstract":"As the most versatile and precise gene editing technology, prime editing (PE) can establish a durable cure for most human genetic disorders. Several generations of PE have been developed based on an editor machine or prime editing guide RNA (pegRNA) to achieve any kind of genetic correction. However, due to the early stage of development, PE complex elements need to be optimized for more efficient editing. Smart optimization of editor proteins as well as pegRNA has been contemplated by many researchers, but the universal PE machine's current shortcomings remain to be solved. The modification of PE elements, fine-tuning of the host genes, manipulation of epigenetics, and blockage of immune responses could be used to reach more efficient PE. Moreover, the host factors involved in the PE process, such as repair and innate immune system genes, have not been determined, and PE cell context dependency is still poorly understood. Regarding the large size of the PE elements, delivery is a significant challenge and the development of a universal viral or nonviral platform is still far from complete. PE versions with shortened variants of reverse transcriptase are still too large to fit in common viral vectors. Overall, PE faces challenges in optimization for efficiency, high context dependency during the cell cycling, and delivery due to the large size of elements. In addition, immune responses, unpredictability of outcomes, and off-target effects further limit its application, making it essential to address these issues for broader use in nonpersonalized gene editing. Besides, due to the limited number of suitable animal models and computational modeling, the prediction of the PE process remains challenging. In this review, the fundamentals of PE, including generations, potential, optimization, delivery, in vivo barriers, and the future landscape of the technology are discussed.","PeriodicalId":13007,"journal":{"name":"Human gene therapy","volume":" ","pages":"649-668"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237794","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