Adeno-Associated Virus 5 Transduces Adipose-Derived Stem Cells with Greater Efficacy Than Other Adeno-Associated Viral Serotypes.
Adeno-Associated Virus 5 Transduces Adipose-Derived Stem Cells with Greater Efficacy Than Other Adeno-Associated Viral Serotypes.
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DOI：
10.1089/hgtb.2016.123
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发表时间：
2016-12
影响因子：
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通讯作者：
Priyanka Sharma;S. Wimalawansa;Gregory C. Gould;R. Johnson;K. Excoffon
中科院分区：
文献类型：
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作者：
Priyanka Sharma;S. Wimalawansa;Gregory C. Gould;R. Johnson;K. Excoffon
脂肪源性干细胞（ASC）已显示出治疗无数疾病的潜力;然而，单独输注细胞不太可能提供全部潜在的治疗应用。ASC的瞬时遗传操作可以在特定疾病背景下增加它们的修复和再生特性，基本上将它们转化为药物洗脱仓库。本研究的目的是确定用重组腺相关病毒（rAAV）治疗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。在这项研究中，最常见的重组AAV载体的基因表达的转导和持续时间进行了测试。在所有测试的血清型中，rAAV 5导致最高和最长期限的表达。此外，我们确定了神经氨酸酶处理前后ASC的糖基化谱，并证明rAAV 5转导需要质膜相关的唾液酸。未来的研究将集中在优化基因递送到ASC，使用rAAV 5作为选择的载体，以驱动生物药物递送，植入和疾病矫正。
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.