title: Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells.
abstract: The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use of siRNA in research and therapy; among the most notable of these is clinically relevant delivery into cells. To address this problem, we designed and synthesized the first members of a new class of guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, and release siRNA in cells, resulting in robust knockdown of target protein synthesis in vitro as determined using a dual-reporter system. The organocatalytic oligomerization used to synthesize these co-oligomers is step-economical and broadly tunable, affording an exceptionally quick strategy to explore chemical space for optimal siRNA delivery in varied applications. The speed and versatility of this approach and the biodegradability of the designed agents make this an attractive strategy for biological tool development, imaging, diagnostics, and therapeutic applications.
authors: Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
authors: Erika I
authors: EI
authors: Geihe
authors: Christina B
authors: CB
authors: Cooley
authors: Jeff R
authors: JR
authors: Simon
authors: Matthew K
authors: MK
authors: Kiesewetter
authors: Justin A
authors: JA
authors: Edward
authors: Robyn P
authors: RP
authors: Hickerson
authors: Roger L
authors: RL
authors: Kaspar
authors: James L
authors: JL
authors: Hedrick
authors: Robert M
authors: RM
authors: Waymouth
authors: Paul A
authors: PA
authors: Wender
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D002254:Carbonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019791:Guanidine / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008027:Light; D018551:Solanum lycopersicum / Q000378:metabolism; D008856:Microscopy, Fluorescence; D034741:RNA, Small Interfering / Q000378:metabolism* / Q000633:toxicity; D012542:Scattering, Radiation
chemical_list: D002254:Carbonates; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019791:Guanidine