经自我互补型腺相关病毒载体对马关节组织进行的体外血清型特异性转导。
Ex vivo serotype-specific transduction of equine joint tissue by self-complementary adeno-associated viral vectors.
机构信息
Orthopaedic Research Center, College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA.
出版信息
Hum Gene Ther. 2009 Dec;20(12):1697-702. doi: 10.1089/hum.2009.030.
Abstract
Cell transplantation for the treatment of joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of joint tissue cells with various adeno-associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in joint tissue containing chondrocytes and synoviocytes isolated from equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2, and serotypes 3 and 2, respectively, appeared superior for gene expression. Unlike adenoviral vectors, no upregulation of inflammatory markers, such as matrix metalloproteinases and aggrecanase, was seen on treatment of joint tissue with AAV vectors ex vivo. Our findings also corroborate that ex vivo transduction of joint tissue can result in high transgene protein levels over time, and transplantation modalities might be feasible using AAV vectors in the treatment of joint-related diseases.
摘要
细胞移植治疗关节疾病是一种重要的临床手段。移植前对细胞进行基因修饰已显示出增强的治疗效果。尚未研究过使用各种腺相关病毒（AAV）血清型对关节组织细胞进行体外基因修饰。本研究旨在确定分离自马模型的包含软骨细胞和滑膜细胞的关节组织中，各种自我互补型 AAV 血清型（1-6 和 8）的转导效率。在比较用于体外高效转导的 scAAV 血清型时，与滑膜细胞相比，血清型 6 和 2 以及血清型 3 和 2 分别在基因表达方面表现出更高的优势。与腺病毒载体不同，体外使用 AAV 载体处理关节组织不会引起基质金属蛋白酶和聚集素酶等炎症标志物的上调。我们的研究结果还证实，体外转导关节组织可以随着时间的推移导致转基因蛋白水平升高，并且使用 AAV 载体进行移植可能是治疗关节相关疾病的可行方法。
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