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中文摘要：
我们设计合成了特异性靶向乙型肝炎病毒（HBV）mRNA的反义RNA寡核苷酸P．2987、X．60和X．519．在瞬时转染pHBVl．3质粒（含有1．3拷贝的HBV基因组）的HepG2细胞和整合了HBV基因组的HepG2．2．15细胞中，转染2lμmol/L的反义RNA寡核苷酸，ELISA和实时定量PCR结果表明，这3条寡核苷酸可以明显抑制HBV的复制和抗原表达．在HBV转基因鼠中，尾静脉注射反义RNA寡核苷酸，结果表明，肝脏中HBV的复制得到了抑制，但是血清中抗原含量和HBVDNA拷贝数没有明显变化．反义RNA寡核苷酸X．519与脂质体的复合物可以增强其对于HBV在肝脏中复制的抑制作用．在通过高压尾静脉注射pHBV1．3质粒建立的HBV急性感染模型中，反义RNA寡核苷酸X．519可以显著地抑制I-IBV在肝脏中的复制以及降低血清中病毒抗原水平和DNA拷贝数．上述实验结果说明，X．519及其与脂质体的复合物对于HBV的复制和抗原表达起到明显的抑制作用，可能作为一种潜在的针对HBV的基因治疗药物．
英文摘要：
We investigated the inhibitory effect of modified antisense RNA oligonucleotides and cationic liposome-RNA complexes on the repression of hepatitis B virus （HBV） replication and expression. ELISA and quantitative Real-time PCR analysis showed that HBV replication and antigens expression both in pHBV1.3 transduced HepG2 and HepG2.2.15 cells were reduced after treatment with antisense RNA oligonucleotides P-2987, X-60 and X-519. Subsequently, the antisense RNA oligonucleotides and control RNA oligonucleotides were injected via the tail vein into I-IBV transgenic mice or hydrodynamically injected mice. In the HBV transgenic mice, with the treatment of X-519, HBV pregenomic RNA in the liver decreased by 81%. Cationic liposome further increased the inhibition effectory to 91%. But no significant differences were observed for HBV antigens and HBV DNA copy number in the sera. In acute HBV infection mouse model by hydrodynamic injection, ELISA and quantitative real-time PCR analysis showed that X-519 significantly repressed HBV replication, as measured by HBV pregenomic RNA, antigens expression, and presence of HBV DNA in the sera. Taken together, the synthesized antisense RNA oligonucleotide X-519 repressed HBV replication and antigens expression in vitro and in vivo.
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