Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA

Publication date: Available online 28 December 2016 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Jayesh A. Kulkarni, J. Layne Myhre, Sam Chen, Yuen Yi C. Tam, Adrian Danescu, Joy M. Richman, Pieter R. Cullis Lipid nanoparticles (LNPs) containing distearolyphosphatidlycholine (DSPC), and ionizable amino-lipids such as (6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl-4-(dimethylamino)butanoate (DLin-MC3-DMA) are potent siRNA delivery vehicles in vivo. Here we explore the utility of similar LNP systems as transfection reagents for plasmid DNA (pDNA). It is shown that replacement of DSPC by unsaturated PCs and DLin-MC3-DMA by the related lipid DLin-KC2-DMA resulted in highly potent transfection reagents for HeLa cells in vitro. Further, these formulations exhibited excellent transfection properties in a variety of mammalian cell lines and transfection efficiencies approaching 90% in primary cell cultures. These transfection levels were equal or greater than achieved by Lipofectamine, with much reduced toxicity. Finally, microinjection of LNP-eGFP into the limb bud of a chick embryo resulted in robust reporter-gene expression. It is concluded that LNP systems containing ionizable cationic lipids can be highly effective, non-toxic pDNA delivery systems for gene expression both in vitro and in vivo. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research