The article introduces a novel method for inhibiting microRNAs (miRNAs) in mammalian cells using "microRNA sponges." These sponges are designed as transcripts expressed from strong promoters, containing multiple tandem binding sites for a specific miRNA. The authors demonstrate that these sponges can effectively derepress miRNA targets in cultured cells, with activity comparable to chemically modified antisense oligonucleotides. The sponges are specific to miRNA seed families, allowing a single sponge to block an entire family of miRNAs. The study also shows that sponges can be used to validate predicted miRNA targets and to assay loss-of-function phenotypes. The authors envision the use of stably expressed sponges in animal models to investigate the roles of miRNAs in disease and development. The article includes detailed methods for constructing and testing the sponges, as well as supplementary figures and references.The article introduces a novel method for inhibiting microRNAs (miRNAs) in mammalian cells using "microRNA sponges." These sponges are designed as transcripts expressed from strong promoters, containing multiple tandem binding sites for a specific miRNA. The authors demonstrate that these sponges can effectively derepress miRNA targets in cultured cells, with activity comparable to chemically modified antisense oligonucleotides. The sponges are specific to miRNA seed families, allowing a single sponge to block an entire family of miRNAs. The study also shows that sponges can be used to validate predicted miRNA targets and to assay loss-of-function phenotypes. The authors envision the use of stably expressed sponges in animal models to investigate the roles of miRNAs in disease and development. The article includes detailed methods for constructing and testing the sponges, as well as supplementary figures and references.