RNA干扰在白血病基因治疗中的应用前景

The potential of gene therapy of leukemia with RNA interference

RNA干扰（RNAi）作为一种进化保守的转录后基因沉默机制，是指双链RNA分子（dsRNA）被切割成21-23个核苷酸的小干扰RNA（siRNA），最终使其同源的mRNA特异性降解。RNAi现广泛用于多个生物体的功能基因组学研究，以及在基因表达异常导致的多种疾病的临床前模型中进行干预治疗。大约50％的白血病伴有异常基因的表达，利用RNAi肿瘤特异性基因靶向治疗为治疗白血病提供了一条新途径。随着siRNA在活体中的稳定性和转染效率的提高、非特异性作用的减少，正迅速应用于临床中。

RNA interference （ RNAi ） as an evolutionary highly conserved process of post-transcriptional gene silencing is that long double-stranded RNA molecules are processed to generate 21 - 23 nucleotide small double-stranded interfering RNAs （ siRNAs ） which mediates sequence-specific degradation of the sequence-homologous mRNA. RNAi is currently used for both systematic functional genomics in several organisms and for specific therapeutic intervention in preclinical models of different diseases characterized by aberrant gene expression. About 50% of all leukemia cases are associated with aberrant gene expression, targeting tumor-specific genes provide a new way for gene therapy of leukemia. The development of RNAi-based reagents for clinical applications is gathering pace, as technique to improve siRNA stability and delivery in vivo is enhanced, and nonspecific effects are minimized.