生物
小RNA
RNA干扰
基因敲除
计算生物学
基因沉默
基因
小干扰RNA
合理设计
遗传学
转染
核糖核酸
作者
Zhou Jiang,Wei Jun Liu,Yuhui Wang,Zhen Gao,Ge Gao,Xiaowei Wang
出处
期刊:RNA
日期:2013-10-21
卷期号:19 (12): 1745-1754
被引量:10
标识
DOI:10.1261/rna.039677.113
摘要
MicroRNAs (miRNAs) are involved in a variety of human diseases by simultaneously suppressing many gene targets. Thus, the therapeutic value of miRNAs has been intensely studied. However, there are potential limitations with miRNA-based therapeutics such as a relatively moderate impact on gene target regulation and cellular phenotypic control. To address these issues, we proposed to design new chimeric small RNAs (aiRNAs) by incorporating sequences from both miRNAs and siRNAs. These aiRNAs not only inherited functions from natural miRNAs, but also gained new functions of gene knockdown in an siRNA-like fashion. The improved efficacy of multifunctional aiRNAs was demonstrated in our study by design and testing of an aiRNA that inherited the functions of both miR-200a and an AKT1-targeting siRNA for simultaneous suppression of cancer cell motility and proliferation. The general principles of aiRNA design were further validated by engineering new aiRNAs mimicking another miRNA, miR-9. By regulating multiple cellular functions, aiRNAs could be used as an improved tool over miRNAs to target disease-related genes, thus alleviating our dependency on a limited number of miRNAs for the development of RNAi-based therapeutics.
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