ANTI SENSE INHIBITION OF HBSAG EXPRESSION IN HEP G2 CELL

描述(改编自申请人摘要)：唯一修改 针对乙肝表面的反义寡核苷酸 抗原转录物将在分化的肝癌细胞系中进行评估 这支持了具有传染性的丹麦粒子的构成生产。 将通过分析监测表面抗原产生的抑制情况 使用商品化的乙肝表面抗原的等量介质 可用的酶联免疫吸附试验试剂盒。要审查的ODN修改将包括 烷基侧臂终止于氨基、胆固醇或吖啶基团。 这些臂将单独或组合在5‘、3’和 ODN的内部站点。选定的ODN将与 去唾液酸类粘液-多-L-赖氨酸结合物先前显示促进 受体介导的DNA在肝细胞内的内化。的影响 这种递送系统对反义效应的效力和对 将确定每个ODN的稳定性和细胞摄取。

DESCRIPTION (Adapted from applicant's abstract): Uniquely modified anti-sense oligodeoxynucleotides (ODNs) targeted to the hepatitis B surface antigen transcript will be evaluated in a differentiated hepatoma cell line which supports the constituitive production of infectious Dane particles. Inhibition of surface antigen production will be monitored by analyzing aliquots of the media for hepatitis B surface antigen using a commercially available ELISA kit. ODN modifications to be examined will consist of alkyl side arms terminating in amino, cholesterol, or acridine groups. These arms will be introduced singly or in combination at 5', 3', and internal sites of the ODN. Selected ODNs will be complexed with an asialoorosomucoid-poly-L-lysine conjugate previously shown to promote receptor-mediated internalization of DNA in hepatocytes. The effect of this delivery system on the potency of the anti-sense effect and on the stability and cellular uptake of each ODN will be determined.