Adeno-Associated Virus 5 Transduces Adipose-Derived Stem Cells with Greater Efficacy Than Other Adeno-Associated Viral Serotypes.

Q1 Immunology and Microbiology

Human Gene Therapy Methods Pub Date : 2016-12-01 DOI:10.1089/HGTB.2016.123

Priyanka Sharma, S. Wimalawansa, Gregory C. Gould, R. Johnson, K. Excoffon

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引用次数: 3

Abstract

Adipose-derived stem cells (ASCs) have shown potential in the treatment of a myriad of diseases; however, infusion of cells alone is unlikely to provide the full range of potential therapeutic applications. Transient genetic manipulation of ASCs could increase their repair and regeneration characteristics in a disease-specific context, essentially transforming them into drug-eluting depots. The goal of this study was to determine the optimal parameters necessary to transduce ASCs with recombinant adeno-associated virus (rAAV), an approved gene therapy vector that has never been associated with disease. Transduction and duration of gene expression of the most common recombinant AAV vectors were tested in this study. Among all tested serotypes, rAAV5 resulted in both the highest and longest term expression. Furthermore, we determined the glycosylation profile of ASCs before and after neuraminidase treatment and demonstrate that rAAV5 transduction requires plasma membrane-associated sialic acid. Future studies will focus on the optimization of gene delivery to ASCs, using rAAV5 as the vector of choice, to drive biological drug delivery, engraftment, and disease correction.

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腺相关病毒5比其他腺相关病毒血清型更有效地转导脂肪来源的干细胞。

脂肪源性干细胞(ASCs)已显示出治疗多种疾病的潜力;然而，单独的细胞输注不太可能提供全面的潜在治疗应用。对ASCs的短暂遗传操作可以增加其在特定疾病环境下的修复和再生特性，从本质上将其转化为药物洗脱库。本研究的目的是确定用重组腺相关病毒(rAAV)转导ASCs所需的最佳参数，rAAV是一种批准的基因治疗载体，从未与疾病相关。本研究检测了最常见的重组AAV载体的转导和基因表达时间。在所有检测的血清型中，rAAV5的表达量最高，表达期最长。此外，我们测定了神经氨酸酶治疗前后ASCs的糖基化谱，并证明rAAV5的转导需要质膜相关唾液酸。未来的研究将集中于优化ASCs的基因传递，以rAAV5为载体，驱动生物药物传递、植入和疾病纠正。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Gene Therapy Methods BIOTECHNOLOGY & APPLIED MICROBIOLOGY-GENETICS & HEREDITY

CiteScore

5.80

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases. The Journal is divided into three parts. Human Gene Therapy, the flagship, is published 12 times per year. HGT Methods, a bimonthly journal, focuses on the applications of gene therapy to product testing and development. HGT Clinical Development, a quarterly journal, serves as a venue for publishing data relevant to the regulatory review and commercial development of cell and gene therapy products.