Advances in AAV-mediated gene replacement therapy for pediatric monogenic neurological disorders.

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Therapy-Methods & Clinical Development Pub Date : 2024-10-16 eCollection Date: 2024-12-12 DOI:10.1016/j.omtm.2024.101357

Livia Zhou, Yafeng Wang, Yiran Xu, Yaodong Zhang, Changlian Zhu

{"title":"Advances in AAV-mediated gene replacement therapy for pediatric monogenic neurological disorders.","authors":"Livia Zhou, Yafeng Wang, Yiran Xu, Yaodong Zhang, Changlian Zhu","doi":"10.1016/j.omtm.2024.101357","DOIUrl":null,"url":null,"abstract":"<p><p>Pediatric monogenetic diseases encompass a spectrum of debilitating neurological disorders that affect infants and children, often resulting in profound cognitive and motor impairments. Gene replacement therapy holds immense promise in addressing the underlying genetic defects responsible for these conditions. Adeno-associated virus (AAV) vectors have emerged as a leading platform for delivering therapeutic genes due to their safety profile and ability to transduce various cell types, including neurons. This review highlights recent advancements in AAV-mediated gene replacement therapy for pediatric monogenetic diseases, focusing on key preclinical and clinical studies. We discuss various strategies to enhance transduction efficiency, target specificity, and safety. Furthermore, we explore challenges such as immune responses, along with innovative approaches to overcome these obstacles. Moreover, we examine the clinical outcomes and safety profiles of AAV-based gene therapies in pediatric patients, providing insights into the feasibility and efficacy of these interventions. Finally, we discuss future directions and potential avenues for further research to optimize the therapeutic potential of AAV-delivered gene replacement therapy for pediatric encephalopathies, ultimately aiming to improve the quality of life for affected individuals and their families.</p>","PeriodicalId":54333,"journal":{"name":"Molecular Therapy-Methods & Clinical Development","volume":"32 4","pages":"101357"},"PeriodicalIF":4.6000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570947/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy-Methods & Clinical Development","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.omtm.2024.101357","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/12 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Pediatric monogenetic diseases encompass a spectrum of debilitating neurological disorders that affect infants and children, often resulting in profound cognitive and motor impairments. Gene replacement therapy holds immense promise in addressing the underlying genetic defects responsible for these conditions. Adeno-associated virus (AAV) vectors have emerged as a leading platform for delivering therapeutic genes due to their safety profile and ability to transduce various cell types, including neurons. This review highlights recent advancements in AAV-mediated gene replacement therapy for pediatric monogenetic diseases, focusing on key preclinical and clinical studies. We discuss various strategies to enhance transduction efficiency, target specificity, and safety. Furthermore, we explore challenges such as immune responses, along with innovative approaches to overcome these obstacles. Moreover, we examine the clinical outcomes and safety profiles of AAV-based gene therapies in pediatric patients, providing insights into the feasibility and efficacy of these interventions. Finally, we discuss future directions and potential avenues for further research to optimize the therapeutic potential of AAV-delivered gene replacement therapy for pediatric encephalopathies, ultimately aiming to improve the quality of life for affected individuals and their families.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

AAV 介导的小儿单基因神经系统疾病基因替代疗法的进展。

小儿单基因遗传病包括一系列影响婴幼儿的神经系统衰弱性疾病，通常会导致严重的认知和运动障碍。基因替代疗法在解决导致这些疾病的潜在基因缺陷方面前景广阔。腺相关病毒（AAV）载体因其安全性和转导包括神经元在内的各种细胞类型的能力，已成为提供治疗基因的主要平台。本综述将重点介绍 AAV 介导的小儿单基因遗传病基因替代疗法的最新进展，重点关注关键的临床前和临床研究。我们讨论了提高转导效率、靶向特异性和安全性的各种策略。此外，我们还探讨了免疫反应等挑战，以及克服这些障碍的创新方法。此外，我们还考察了基于 AAV 的基因疗法在儿科患者中的临床结果和安全性，从而深入了解这些干预措施的可行性和有效性。最后，我们讨论了进一步研究的未来方向和潜在途径，以优化 AAV 运载基因替代疗法对小儿脑病的治疗潜力，最终改善患者及其家庭的生活质量。

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分钟内获得全文去求助

来源期刊

Molecular Therapy-Methods & Clinical Development Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.90

自引率

4.30%

发文量

163

审稿时长

12 weeks

期刊介绍： The aim of Molecular Therapy—Methods & Clinical Development is to build upon the success of Molecular Therapy in publishing important peer-reviewed methods and procedures, as well as translational advances in the broad array of fields under the molecular therapy umbrella. Topics of particular interest within the journal''s scope include: Gene vector engineering and production, Methods for targeted genome editing and engineering, Methods and technology development for cell reprogramming and directed differentiation of pluripotent cells, Methods for gene and cell vector delivery, Development of biomaterials and nanoparticles for applications in gene and cell therapy and regenerative medicine, Analysis of gene and cell vector biodistribution and tracking, Pharmacology/toxicology studies of new and next-generation vectors, Methods for cell isolation, engineering, culture, expansion, and transplantation, Cell processing, storage, and banking for therapeutic application, Preclinical and QC/QA assay development, Translational and clinical scale-up and Good Manufacturing procedures and process development, Clinical protocol development, Computational and bioinformatic methods for analysis, modeling, or visualization of biological data, Negotiating the regulatory approval process and obtaining such approval for clinical trials.