Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps

IF 3.4 3区 医学 Q2 HEMATOLOGY
Wolfgang Miesbach , Paul Batty , Pratima Chowdary , Sylvia Fong , Radoslaw Kaczmarek , Frank W.G. Leebeek , Brian Long , Johnny Mahlangu , Mike Makris , Glenn F. Pierce , Steven W. Pipe , Alok Srivastava , Jan Voorberg , Flora Peyvandi
{"title":"Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps","authors":"Wolfgang Miesbach ,&nbsp;Paul Batty ,&nbsp;Pratima Chowdary ,&nbsp;Sylvia Fong ,&nbsp;Radoslaw Kaczmarek ,&nbsp;Frank W.G. Leebeek ,&nbsp;Brian Long ,&nbsp;Johnny Mahlangu ,&nbsp;Mike Makris ,&nbsp;Glenn F. Pierce ,&nbsp;Steven W. Pipe ,&nbsp;Alok Srivastava ,&nbsp;Jan Voorberg ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2024.102673","DOIUrl":null,"url":null,"abstract":"<div><div>Adeno-associated virus-based gene therapy for hemophilia has emerged as a revolutionary treatment option, offering potential correction of clotting factor deficiency through a single intravenous infusion of functional genes directed to hepatocytes. With 3 gene therapies recently approved, this approach shows promise in transforming the lives of individuals with hemophilia. However, the complexity of gene therapy and the lack of standardization of methods in different components of this therapy can lead to unique challenges for clinical implementation. This manuscript follows literature reviews and structured discussions by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Working Group on Gene Therapy that identified specific areas requiring standardization of methods, including viral vector production, liver function assessment, quantification of factor (F)VIII and FIX expression levels, assessment of antiadeno-associated viral antibodies, and genomic integration detection methods. Standardization strategies aim to achieve consistent vector quality, effective patient selection, and uniform assessment methods by implementing advanced laboratory techniques and standardized protocols. Standardizing these parameters is essential for improving the understanding of short-term and long-term safety and efficacy of gene therapy in hemophilia. This effort aims to enhance the predictability of individual responses, address variability in outcomes, and ultimately provide more effective, safer, and personalized treatment options for individuals with hemophilia.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102673"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787635/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research and Practice in Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2475037924003686","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Adeno-associated virus-based gene therapy for hemophilia has emerged as a revolutionary treatment option, offering potential correction of clotting factor deficiency through a single intravenous infusion of functional genes directed to hepatocytes. With 3 gene therapies recently approved, this approach shows promise in transforming the lives of individuals with hemophilia. However, the complexity of gene therapy and the lack of standardization of methods in different components of this therapy can lead to unique challenges for clinical implementation. This manuscript follows literature reviews and structured discussions by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Working Group on Gene Therapy that identified specific areas requiring standardization of methods, including viral vector production, liver function assessment, quantification of factor (F)VIII and FIX expression levels, assessment of antiadeno-associated viral antibodies, and genomic integration detection methods. Standardization strategies aim to achieve consistent vector quality, effective patient selection, and uniform assessment methods by implementing advanced laboratory techniques and standardized protocols. Standardizing these parameters is essential for improving the understanding of short-term and long-term safety and efficacy of gene therapy in hemophilia. This effort aims to enhance the predictability of individual responses, address variability in outcomes, and ultimately provide more effective, safer, and personalized treatment options for individuals with hemophilia.
基于腺相关病毒的血友病基因治疗——填补空白。
基于腺相关病毒的血友病基因治疗已成为一种革命性的治疗选择,通过单次静脉输注肝细胞功能基因,提供凝血因子缺乏症的潜在纠正。随着最近批准的3种基因疗法,这种方法有望改变血友病患者的生活。然而,基因治疗的复杂性和这种治疗的不同组成部分缺乏标准化的方法可能导致临床实施的独特挑战。本文遵循国际血栓和止血学会科学和标准化委员会基因治疗工作组的文献综述和结构化讨论,确定了需要标准化方法的特定领域,包括病毒载体产生、肝功能评估、因子(F)VIII和FIX表达水平的量化、抗腺相关病毒抗体的评估和基因组整合检测方法。标准化战略旨在通过实施先进的实验室技术和标准化方案,实现一致的病媒质量、有效的患者选择和统一的评估方法。标准化这些参数对于提高对血友病基因治疗的短期和长期安全性和有效性的理解至关重要。这项工作旨在提高个体反应的可预测性,解决结果的可变性,并最终为血友病患者提供更有效、更安全、更个性化的治疗选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
5.60
自引率
13.00%
发文量
212
审稿时长
7 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信