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

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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。

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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.

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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.