Kumar Lekha Dinesh, Clarke Alan R
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Adv Drug Deliv Rev. 2007 Mar 30;59(2-3):87-100. doi: 10.1016/j.addr.2007.03.009. Epub 2007 Mar 20.
The conventional approach to investigate genotype-phenotype relationships has been the generation of gene targeted murine strains. However, the emergence of RNAi technologies has opened the possibility of much more rapid (and indeed more cost effective) genetic manipulation in vivo at the level of the transcriptome. Successful application of RNAi in vivo depends on intracellular targeted delivery of siRNA/shRNA molecules for efficient knockdown of the desired gene. In this review, we discuss the rationale and different strategies of using siRNA/shRNA for accomplishing the silencing of targeted genes in a spatial and /or temporally regulated manner. We also summarise the steps involved in extending these approaches to in vivo applications, with a specific focus upon the development of silencing in the mouse.
研究基因型与表型关系的传统方法是构建基因靶向小鼠品系。然而，RNA干扰技术的出现为在转录组水平上更快速（且确实更具成本效益）地进行体内基因操作开辟了可能性。RNA干扰在体内的成功应用取决于将小干扰RNA/短发夹RNA分子进行细胞内靶向递送，以有效敲低所需基因。在本综述中，我们讨论了使用小干扰RNA/短发夹RNA以空间和/或时间调控方式实现靶向基因沉默的基本原理和不同策略。我们还总结了将这些方法扩展到体内应用所涉及的步骤，特别关注在小鼠体内实现基因沉默的发展情况。
