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发展了一种高效的、能将携带外源基因的质粒型ＥＢ病毒载体特异性地导入肝细胞表达的方法。将ＥＢ病毒复制子载体ｐＤＲ２经改造得到携带外源基因的ｐＥＢｌｕｃ质粒。将ｐＥＢｌｕｃ与人工制备的、既保留了ＤＮＡ结合活性又能为肝细胞受体识别并内在化的半乳糖基化组蛋白的ｆｌ组分结合，形成ｐＥＢｌｕｃ－半乳糖基化组蛋白复合物。该复合物通过脱唾液酸糖蛋白受体介导的内吞进入肝细胞并表达。ｐＥＢｌｕｃ质粒在细胞内能稳定存在并自主复制。该系统具有应用于以肝细胞为靶组织的基因治疗的前景。
A highly efficient method of introducing plasmid-borne Epstein-Barr virus vectors carrying exogenous genes into hepatocytes has been developed. The Epstein-Barr virus replicon vector pDR2 was engineered to produce the pEBluc plasmid carrying the exogenous gene. The pEBluc is combined with an artificially prepared fl component of a galactosylated histone that retains DNA-binding activity and which recognizes and internalizes the hepatocyte receptor to form a pEBluc-galactosylated histone complex. The complex is endocytosed into hepatocytes and expressed by asialoglycoprotein receptor-mediated endocytosis. pEBluc plasmid in the cell can exist stably and autonomously. The system has the prospect of gene therapy applied to hepatocytes as a target tissue.