Cellular Delivery of siRNAs Using Bolaamphiphiles
1RNA Structure and Design Section, RNA Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, 21702, MD, USA. kshitijgupta@ipc.iisc.ernet.in.
Abstract:
Discovery of RNA interference (RNAi) has opened up a new arena of therapeutic intervention for the treatment of cancerous as well as noncancerous diseases. The RNAi pathway utilizes RNAi inducers such as small interfering RNAs (siRNAs) to target and silence disease causing genes. However, efficient delivery of siRNAs for eliciting efficacious RNAi has remained a daunting challenge. Nonviral vectors such as lipids have shown great promise in delivering siRNAs. Recently, a novel class of cationic lipid molecules "bolaamphiphile lipids" or "bola lipids" has been shown to deliver siRNAs to cause effective gene silencing in cells. The present chapter showcases the ability of bola lipids to form micelles, bind with nucleic acids and protect nucleic acids against nucleases. Also, high in vitro transfection efficiency for silencing green fluorescent protein (GFP) using Dicer substrate siRNAs (dsiRNAs) designed against GFP at nontoxic dose in a human breast cancer model is demonstrated. Our results showed that these cationic bola lipids are promising siRNA delivery agents.
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