对人类许旺细胞具有更好趋向性的新型 AAV 变体

IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Therapy-Methods & Clinical Development Pub Date : 2024-03-11 DOI:10.1016/j.omtm.2024.101234
Matthieu Drouyer, Tak-Ho Chu, Elodie Labit, Florencia Haase, Renina Gale Navarro, Deborah Nazareth, Nicole Rosin, Jessica Merjane, Suzanne Scott, Marti Cabanes-Creus, Adrian Westhaus, Erhua Zhu, Rajiv Midha, Ian E. Alexander, Jeff Biernaskie, Samantha L. Ginn, Leszek Lisowski
{"title":"对人类许旺细胞具有更好趋向性的新型 AAV 变体","authors":"Matthieu Drouyer, Tak-Ho Chu, Elodie Labit, Florencia Haase, Renina Gale Navarro, Deborah Nazareth, Nicole Rosin, Jessica Merjane, Suzanne Scott, Marti Cabanes-Creus, Adrian Westhaus, Erhua Zhu, Rajiv Midha, Ian E. Alexander, Jeff Biernaskie, Samantha L. Ginn, Leszek Lisowski","doi":"10.1016/j.omtm.2024.101234","DOIUrl":null,"url":null,"abstract":"Gene therapies and associated technologies are transforming biomedical research and enabling novel therapeutic options for patients living with debilitating and incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials for genetic diseases of multiple organs, such as the liver and the nervous system. Despite recent successes toward the development of novel bioengineered AAV variants for improved transduction of primary human tissues and cells, vectors that can efficiently transduce human Schwann cells (hSCs) have yet to be identified. Here, we report the application of the functional transduction-RNA selection method in primary hSCs for the development of bespoke AAV variants for specific and efficient transgene delivery to hSCs. The two identified capsid variants, Pep2hSC1 and Pep2hSC2, show conserved potency for delivery across various , , and models of hSCs. These novel AAV capsids will serve as valuable research tools, forming the basis for therapeutic solutions for both SC-related disorders or peripheral nervous system injury.","PeriodicalId":54333,"journal":{"name":"Molecular Therapy-Methods & Clinical Development","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel AAV variants with improved tropism for human Schwann cells\",\"authors\":\"Matthieu Drouyer, Tak-Ho Chu, Elodie Labit, Florencia Haase, Renina Gale Navarro, Deborah Nazareth, Nicole Rosin, Jessica Merjane, Suzanne Scott, Marti Cabanes-Creus, Adrian Westhaus, Erhua Zhu, Rajiv Midha, Ian E. Alexander, Jeff Biernaskie, Samantha L. Ginn, Leszek Lisowski\",\"doi\":\"10.1016/j.omtm.2024.101234\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Gene therapies and associated technologies are transforming biomedical research and enabling novel therapeutic options for patients living with debilitating and incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials for genetic diseases of multiple organs, such as the liver and the nervous system. Despite recent successes toward the development of novel bioengineered AAV variants for improved transduction of primary human tissues and cells, vectors that can efficiently transduce human Schwann cells (hSCs) have yet to be identified. Here, we report the application of the functional transduction-RNA selection method in primary hSCs for the development of bespoke AAV variants for specific and efficient transgene delivery to hSCs. The two identified capsid variants, Pep2hSC1 and Pep2hSC2, show conserved potency for delivery across various , , and models of hSCs. These novel AAV capsids will serve as valuable research tools, forming the basis for therapeutic solutions for both SC-related disorders or peripheral nervous system injury.\",\"PeriodicalId\":54333,\"journal\":{\"name\":\"Molecular Therapy-Methods & Clinical Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-03-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Therapy-Methods & Clinical Development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.omtm.2024.101234\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy-Methods & Clinical Development","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.omtm.2024.101234","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

基因疗法和相关技术正在改变生物医学研究,并为衰弱和无法治愈的遗传疾病患者提供了新的治疗方案。以重组腺相关病毒载体(AAV)为基础的载体系统在最近的临床试验中显示出治疗肝脏和神经系统等多器官遗传疾病的巨大前景。尽管最近在开发新型生物工程 AAV 变体以改善原代人体组织和细胞的转导方面取得了成功,但能有效转导人许旺细胞(hSCs)的载体仍有待鉴定。在此,我们报告了在原代间充质干细胞中应用功能性转导-RNA选择方法开发定制AAV变体,以特异、高效地向间充质干细胞传递转基因。两种已鉴定的病毒壳变体--Pep2hSC1 和 Pep2hSC2--显示出在不同的造血干细胞模型中具有一致的转导效力。这些新型 AAV 胶囊将成为有价值的研究工具,为 SC 相关疾病或外周神经系统损伤的治疗方案奠定基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Novel AAV variants with improved tropism for human Schwann cells
Gene therapies and associated technologies are transforming biomedical research and enabling novel therapeutic options for patients living with debilitating and incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials for genetic diseases of multiple organs, such as the liver and the nervous system. Despite recent successes toward the development of novel bioengineered AAV variants for improved transduction of primary human tissues and cells, vectors that can efficiently transduce human Schwann cells (hSCs) have yet to be identified. Here, we report the application of the functional transduction-RNA selection method in primary hSCs for the development of bespoke AAV variants for specific and efficient transgene delivery to hSCs. The two identified capsid variants, Pep2hSC1 and Pep2hSC2, show conserved potency for delivery across various , , and models of hSCs. These novel AAV capsids will serve as valuable research tools, forming the basis for therapeutic solutions for both SC-related disorders or peripheral nervous system injury.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Molecular Therapy-Methods & Clinical Development
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.
期刊最新文献
What's in a word? Defining "gene therapy medicines". Comparison and cross-validation of long-read and short-read target-enrichment sequencing methods to assess AAV vector integration into host genome. Toward a translational gene therapy for mucolipidosis IV. Identification of a novel neutralization epitope in rhesus AAVs. AAVolve: Concatenated long-read deep sequencing enables whole capsid tracking during shuffled AAV library selection.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1