title: Design and assembly of new nonviral RNAi delivery agents by microwave-assisted quaternization (MAQ) of tertiary amines.
abstract: RNA interference (RNAi) is a gene-silencing phenomenon whereby double-stranded RNA (dsRNA) triggers the sequence-specific degradation of homologous mRNA. RNAi has been quickly and widely applied to discover gene functions and holds great potential to provide a new class of therapeutic agents. However, new chemistry and delivery approaches are greatly needed to silence disease-causing genes without toxic effects. We reasoned that conjugation of the cholesterol moiety to cationic lipids would enhance RNAi efficiencies and lower the toxic effects of lipid-mediated RNAi delivery. Here, we report the first design and synthesis of new cholesterol-conjugated cationic lipids for RNAi delivery using microwave-assisted quaternization (MAQ) of tertiary amines. This strategy can be employed to develop new classes of nonviral gene delivery agents under safe and fast reaction conditions.
authors: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Animesh
authors: A
authors: Ghosh
authors: Koushik
authors: K
authors: Mukherjee
authors: Xinpeng
authors: X
authors: Jiang
authors: Ying
authors: Y
authors: Zhou
authors: Joshua
authors: J
authors: McCarroll
authors: James
authors: J
authors: Qu
authors: Pamela M
authors: PM
authors: Swain
authors: Huricha
authors: H
authors: Baigude
authors: Tariq M
authors: TM
authors: Rana
mesh_terms: D000588:Amines / Q000737:chemistry*; D002412:Cations; D002784:Cholesterol / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry; D008872:Microwaves; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D000588:Amines; D002412:Cations; D008055:Lipids; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002784:Cholesterol