基因药物研究现状和对策

Advances and Strategies in Gene Drugs Development

生物技术药物以人类体细胞的基因组、转录本组和蛋白质组三个层次生物大分子为目标 ,基因药物的研究主要针对致病基因的DNA和基因转录本mRNA两类生物大分子 .mRNA从结构上考虑是研发核酸药物的最理想靶标和策略之一 .反义寡核苷酸、特异水解基因mRNA的核酸酶(ribozyme和DNAzyme)以及具有干扰作用的双链RNA(siRNA)是药物设计的策略之二 .mRNA结构靶点研究是研发反mRNA基因药物的基础 ,mRNA分子具有高度折叠的二级及三级结构 ,阐明其可及性位点 ,筛选其结构靶位点序列是关键 .近年研究报道的靶点筛选有约 7种mRNA的实测新技术 ,以及计算机辅助软件预测分析 .但发展分子生物学实验新技术以分析、确认靶点是药物研发策略之三 .

Biotech drugs are targeting DNAs,transcripts and proteins of disease related genes in human cells,among which gene drugs focus on functional gene duplex DNAs and mRNA transcripts.Considering the structure accessibility,mRNA is the first strategy of targeting and the ideal targeting molecule.Hereby antisense oligonucleotides,trans\|cleaving ribozymes or RNA\|cleaving DNAzymes,and siRNAs are the second strategy to design the therapeutic agents.But the structural target sites on mRNA are the basis for developing the anti\|mRNA agents.Since RNA molecules have the secondary and higher structures,to probe the accessibility and verify the accessible sites sequences for targeting is the key challenge.Developing experimental procedures on real mRNA molecules to verify the mRNA accessible sites and confirm the effective binding and targeting is the third strategy.In recent years,seven different approaches based on the real mRNA molecules in vitro were reported for successfully identifying mRNA target sites,while a computer dependent prediction method was also reported.