Cellular Delivery of siRNAs Using Bolaamphiphiles
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.
Key wordsBolaamphiphiles RNAi RNA–DNA hybrids dsiRNAs Green fluorescent protein Human breast cancer cells
This work has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under Contract No. HHSN261200800001E. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. Dr. Kshitij Gupta also acknowledges “Scientist pool officer” position awarded by Council of Scientific and Industrial Research, New Delhi, India and “Young Scientist” award “YSS/2014/000937” by Science and Engineering Research Board, Department of Science & Technology, India.