Design and assembly of new nonviral RNAi delivery agents by microwave-assisted quaternization (MAQ) of tertiary amines.
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.
Ghosh
Animesh
A
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Mukherjee
Koushik
K
Jiang
Xinpeng
X
Zhou
Ying
Y
McCarroll
Joshua
J
Qu
James
J
Swain
Pamela M
PM
Baigude
Huricha
H
Rana
Tariq M
TM
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
D000588:Amines; D002412:Cations; D008055:Lipids; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002784:Cholesterol