The article by Paddison et al. (2002) demonstrates that short hairpin RNAs (shRNAs) can induce sequence-specific silencing in mammalian cells. ShRNAs, which are transcribed from RNA polymerase III promoters or synthesized exogenously, can be used to target and silence specific genes. The authors show that shRNAs are processed by Dicer into 21-nt siRNAs, which then target and degrade complementary target mRNAs. This method of gene silencing is more potent than that achieved using small interfering RNAs (siRNAs) and can be used to create stable and heritable gene silencing in continuous cell lines and transgenic animals. The ability to use shRNAs to silence endogenous genes in mammalian cells opens up new possibilities for studying gene function and for therapeutic applications.The article by Paddison et al. (2002) demonstrates that short hairpin RNAs (shRNAs) can induce sequence-specific silencing in mammalian cells. ShRNAs, which are transcribed from RNA polymerase III promoters or synthesized exogenously, can be used to target and silence specific genes. The authors show that shRNAs are processed by Dicer into 21-nt siRNAs, which then target and degrade complementary target mRNAs. This method of gene silencing is more potent than that achieved using small interfering RNAs (siRNAs) and can be used to create stable and heritable gene silencing in continuous cell lines and transgenic animals. The ability to use shRNAs to silence endogenous genes in mammalian cells opens up new possibilities for studying gene function and for therapeutic applications.