针对普通狨猴大脑皮层特定细胞类型的最佳腺相关病毒壳/启动子组合

IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Yasunori Matsuzaki, Yuuki Fukai, Ayumu Konno, Hirokazu Hirai
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引用次数: 0

摘要

要实现细胞类型特异性基因表达,使用目标细胞类型趋向性不同的腺相关病毒(AAV)外壳是有利的。然而,它们在非人灵长类脑细胞类型中的趋向性尚未完全阐明。我们评估了通过鸡β-肌动蛋白杂交(CBh)启动子表达增强型绿色荧光蛋白(EGFP)的九种AAV血清型(AAV1、2、5、6、7、8、9、rh10和DJ)对狨猴大脑皮层细胞的滋养性。所有九种 AAV 胶囊载体,尤其是 AAV9 和 AAVrh10,都能引起高度神经元选择性的 EGFP 表达。包括 AAV5 在内的一些 AAV 胶囊载体在少突胶质细胞中诱导 EGFP 表达的程度较低。不同的无处不在的巨细胞病毒(CMV)和CMV早期增强子/鸡β肌动蛋白(CAG)启动子表现出类似的以神经元为主的转基因表达。相反,带有星形胶质细胞特异性 hGFA(ABC1D)启动子的所有九种 AAV 胶囊载体都选择性地在星形胶质细胞中表达 EGFP,只有 AAV5 除外,它在少突胶质细胞中适度表达 EGFP。AAV5 载体中的少突胶质细胞特异性小鼠髓鞘碱性蛋白(mMBP)启动子在少突胶质细胞中特异、高效地表达了 EGFP。以下是细胞类型特异性表达的囊壳和启动子的最佳组合:AAV9或AAVrh10和无处不在的CBh或CMV启动子用于神经元特异性转基因表达;AAV2或AAV7和hGFA(ABC1D)启动子用于星形胶质细胞特异性转基因表达;AAV5和mMBP启动子用于少突胶质细胞特异性转基因表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Optimal different adeno-associated virus capsid/promoter combinations to target specific cell types in the common marmoset cerebral cortex

Optimal different adeno-associated virus capsid/promoter combinations to target specific cell types in the common marmoset cerebral cortex

To achieve cell type-specific gene expression, using target cell type-tropic different adeno-associated virus (AAV) capsids is advantageous. However, their tropism across brain cell types in nonhuman primates has not been fully elucidated. We assessed the tropism of nine AAV serotype capsids (AAV1, 2, 5, 6, 7, 8, 9, rh10, and DJ) expressing enhanced green fluorescent protein (EGFP) by chicken β-actin hybrid (CBh) promoter in marmoset cerebral cortical cells. All nine AAV capsid vectors, especially AAV9 and AAVrh10, caused highly neuron-selective EGFP expression. Some AAV capsids, including AAV5, induced EGFP expression to a lesser extent in oligodendrocytes. Different ubiquitous cytomegalovirus (CMV) and CMV early enhancer/chicken β actin (CAG) promoters exhibited similar neuron-predominant transgene expression. Conversely, all nine AAV capsid vectors with the astrocyte-specific hGFA(ABC1D) promoter selectively expressed EGFP in astrocytes, except AAV5, which modestly expressed EGFP in oligodendrocytes. Oligodendrocyte-specific mouse myelin basic protein (mMBP) promoter in AAV5 vectors expressed EGFP in oligodendrocytes specifically and efficiently. The following are optimal combinations of capsids and promoters for cell type-specific expression: AAV9 or AAVrh10 and ubiquitous CBh or CMV promoter for neuron-specific transgene expression; AAV2 or AAV7 and hGFA(ABC1D) promoters for astrocyte-specific transgene expression; and AAV5 and mMBP promoters for oligodendrocyte-specific transgene expression.

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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.
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