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RNAi by feeding larvae with chitosan\/dsRNA nanoparticles led to reductions of <jats:italic>CYP6AA5<\/jats:italic>, <jats:italic>CYP6AL1<\/jats:italic>, <jats:italic>CYP9J32<\/jats:italic>, <jats:italic>CYP4J16A<\/jats:italic>, and <jats:italic>CYP4J16B<\/jats:italic> transcripts by 38.7%, 46.0%, 46.52%, 44.0%, and 41.0%, respectively, and increased larval mortality by 46.0% to permethrin when <jats:italic>CYP9J32<\/jats:italic> was silenced and by 41.2% to cypermethrin when <jats:italic>CYP6AA5<\/jats:italic> was silenced. RNAi by injecting dsRNA in adults led to reductions of <jats:italic>CYP6AA5<\/jats:italic>, <jats:italic>CYP6AL1<\/jats:italic>, and <jats:italic>CY4J16A<\/jats:italic> transcripts by 77.9%, 80.0%, and 87.1% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), respectively, at 96\u2009h and reduction of <jats:italic>CYP9J32<\/jats:italic> transcript by 46.5% at 24\u2009h after injection. In contrast, <jats:italic>CYP4J16B<\/jats:italic> was repressed by 78.2% at 72\u2009h after injection. Exposure of the adults injected with <jats:italic>CYP6AA5<\/jats:italic> dsRNA resulted in 1.5\u2010 to 2.0\u2010fold increased susceptibility to cypermethrin as compared with the control. Homology modeling of CYP6AA5 followed by ligand docking showed that distances between the heme iron and the putative aromatic hydroxylation site were 9.2, 7.2, and 9.1\u2009\u00c5 for permethrin, cypermethrin, and deltamethrin, respectively. For the aliphatic hydroxylation site, these distances were 5.3, 4.9, and 3.1\u2009\u00c5. These results supported that CYP6AA5 may be able to metabolize cypermethrin preferentially by aliphatic hydroxylation as indicated by the close interaction with the heme iron. Our study also suggests that the detoxification roles of cytochrome P450 genes in <jats:italic>A. aegypti<\/jats:italic> may vary according to the mosquito developmental stages, cytochrome P450 genes, and insecticides.<\/jats:p>","DOI":"10.1002\/arch.70013","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T10:52:03Z","timestamp":1733395923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional Roles of Five Cytochrome P450 Transcripts in the Susceptibility of the Yellow Fever Mosquito to Pyrethroids Revealed by RNAi Coupled With Insecticide Bioassay"],"prefix":"10.1002","volume":"117","author":[{"given":"Moustapha","family":"Soumalia Issa","sequence":"first","affiliation":[{"name":"Department of Entomology Kansas State University Manhattan Kansas 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