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核心蛋白聚糖(decorin,DCN)是广泛存在于细胞基质中的一种富含亮氨酸的蛋白多糖,属于蛋白聚糖家族中的小分子类.DCN可作为多种细胞因子的配体,发挥多种生物学功能.DCN在一些肿瘤组织中高水平表达,调控恶性肿瘤的生长和迁移.腺相关病毒(AAV)是肿瘤基因治疗中常用的基因工程载体,利用重组技术可以实现对病毒衣壳蛋白的改造,使其感染具有靶向性.而针对DCN高表达细胞的转导可能成为肿瘤基因治疗应用中定向导入治疗基因的有效策略.本研究在对多种DCN结合蛋白序列保守区的分析基础上,筛选出具有较高活性的DCN结合功能域(DB1),并将其融合至AAV衣壳蛋白VP2编码序列的N端;继而利用AAV的嵌合包装技术,成功制备了衣壳展示DB1表位的重组AAV.在过表达DCN细胞的感染实验中,该病毒表现出针对DCN较强的靶向性.本研究所制备的DCN靶向性腺相关病毒不仅为肿瘤治疗的应用提供了一种新型载体,同时可作为一类特殊的基因导入工具为研究DCN在肿瘤发生发展中的作用提供帮助.
Decorin (DCN) is a leucine-rich proteoglycan which is widely distributed in the cell matrix and belongs to the small class of proteoglycan family.DCN can be used as a ligand for a variety of cytokines, Play a variety of biological functions.DCN expression in some tumor tissues at high levels, regulating the growth and migration of malignant tumors.Adeno-associated virus (AAV) is a gene engineering vector commonly used in cancer gene therapy, the use of recombinant technology can achieve the virus capsid Protein transformation, making it infected with targeting.However, the transduction of highly expressed DCN cells may be an effective strategy for targeted gene therapy in tumor gene therapy.In this study, we analyzed the conserved regions of various DCN binding protein sequences Based on which the DCN binding domain (DB1) with higher activity was screened out and fused to the N-terminal of VP2 coding sequence of AAV capsid protein. Then the capsid display DB1 was successfully prepared by the chimeric packaging technology of AAV Epitope of the recombinant AAV in the over-expression of DCN cell infection experiments, the virus showed a strong targeting of DCN DCN-targeted adeno-associated virus prepared in this study not only for cancer treatment should It provides a new carrier, while as a special kind of gene transfer tools help investigate the role of the development of a tumor occurs in DCN.