title: Dynamic amphiphile libraries to screen for the "fragrant" delivery of siRNA into HeLa cells and human primary fibroblasts.
abstract: Dynamic amphiphiles are amphiphiles with dynamic covalent bridges between their hydrophilic heads and their hydrophobic tails. Their usefulness to activate ion transporters, for odorant release, and for differential sensing of odorants and perfumes, has been demonstrated recently. Here, we report that the same "fragrant" dynamic amphiphiles are ideal to screen for new siRNA transfection agents. The advantages of this approach include rapid access to fairly large libraries of complex structures, and possible transformation en route to assist uptake and minimize toxicity. We report single-component systems that exceed the best commercially available multicomponent cocktails with regard to both efficiency and velocity of EGFP knockdown in HeLa cells. In human primary fibroblasts, siRNA-mediated enzyme knockdown nearly doubled from >30% for Lipofectamine to >60% for our best hit. The identified structures were predictable neither from literature nor from results in fluorogenic vesicles and thus support the importance of conceptually innovative screening approaches.
authors.affiliation: School of Chemistry and Biochemistry, National Centre of Competence in Research (NCCR) Chemical Biology, University of Geneva, Geneva, Switzerland.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gehin
authors.forename: Javier
authors.initials: J
authors.lastname: Montenegro
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Bang
authors.forename: Ana
authors.initials: A
authors.lastname: Cajaraville
authors.forename: Shota
authors.initials: S
authors.lastname: Takayama
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Hirose
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
authors.forename: Stefan
authors.initials: S
authors.lastname: Matile
authors.forename: Howard
authors.initials: H
authors.lastname: Riezman
mesh_terms: D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000378:metabolism*; D013501:Surface-Active Agents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D034741:RNA, Small Interfering; D013501:Surface-Active Agents