siRNA作为基因治疗药物的研究难题

Challenges of RNAi as in vivo gene therapeutic drugs

RNA干扰(RNA i)现象的发现与研究,为基因治疗带来新的契机,虽然小干扰RNA(siRNA)较单链反义寡核苷酸显示了更好的稳定性与基因沉默效果,但却同样面临基因治疗药物存在的共同问题,如体内的靶向性与有效性、完善的定量分析方法等等。因此,siRNA作为治疗药物还有诸多困难需要克服。目前的研究主要集中在:修饰方式与递送系统研究,以提高siRNA体内的稳定性与靶向性;siRNA定量分析方法学研究,以考察其体内药动学行为并进一步阐明其体内作用机制。

The discovery of RNA interference （RNAi） has brought a new chance for gene therapy. Small interfering RNAs （siRNA） have more stability and gene silencing effect than traditional antisense oligo-nucleotides but may not totally abolish common shortfalls of other gene therapy, such as effective targeted delivery in vivo and the appropriate quantification for siRNA. Current challenges of siRNA as therapeutic agents are focusing on the improvements of targeted delivery and stability in vivo by chemical modifications and assessment of pharmacokinetics by establishment of appropriate quantitative assays.