Researchers developed an optimized method for RNA-mediated interference (RNAi) by feeding Caenorhabditis elegans worms with bacteria expressing double-stranded RNA (dsRNA). This method proved as effective as direct injection for inactivating genes, and even more effective for genes with post-embryonic phenotypes. The feeding method allows for titration of RNAi effects, enabling the identification of hypomorphic phenotypes that provide insights into gene function. Using this method, the researchers identified functions for 13 new genes, including two previously uncharacterized genes (ceh-6 and a MADS-box protein) and one gene encoding a novel protein that results in a high-incidence-of-males phenotype. The feeding method is less labor-intensive and more cost-effective than injection, making it suitable for large-scale genetic screens. It is also useful for studying genes that are difficult to analyze using injection or mutants, such as those involved in titration, biochemistry, and large-scale screening. The study demonstrated that RNAi by feeding can produce robust and specific gene inactivation, comparable to injection, and is particularly effective for detecting sterility and post-embryonic phenotypes. The method was validated using a large dataset of genes, showing that RNAi by feeding is as effective as injection for embryonic lethality and slightly better for detecting sterility and post-embryonic phenotypes. The study highlights the potential of RNAi by feeding as a powerful tool for functional genomics in C. elegans.Researchers developed an optimized method for RNA-mediated interference (RNAi) by feeding Caenorhabditis elegans worms with bacteria expressing double-stranded RNA (dsRNA). This method proved as effective as direct injection for inactivating genes, and even more effective for genes with post-embryonic phenotypes. The feeding method allows for titration of RNAi effects, enabling the identification of hypomorphic phenotypes that provide insights into gene function. Using this method, the researchers identified functions for 13 new genes, including two previously uncharacterized genes (ceh-6 and a MADS-box protein) and one gene encoding a novel protein that results in a high-incidence-of-males phenotype. The feeding method is less labor-intensive and more cost-effective than injection, making it suitable for large-scale genetic screens. It is also useful for studying genes that are difficult to analyze using injection or mutants, such as those involved in titration, biochemistry, and large-scale screening. The study demonstrated that RNAi by feeding can produce robust and specific gene inactivation, comparable to injection, and is particularly effective for detecting sterility and post-embryonic phenotypes. The method was validated using a large dataset of genes, showing that RNAi by feeding is as effective as injection for embryonic lethality and slightly better for detecting sterility and post-embryonic phenotypes. The study highlights the potential of RNAi by feeding as a powerful tool for functional genomics in C. elegans.