Enhanced cationic liposome-mediated transfection using the DNA-binding peptide μ (mu) from the adenovirus core

Karl D Murray, C. J. Etheridge, S. I. Shah, D. A. Matthews, W. Russell, H. M D Gurling, A. D. Miller

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Promising advances in nonviral gene transfer have been made as a result of the production of cationic liposomes formulated with synthetic cationic lipids (cytofectins) that are able to transfect cells. However few cationic liposome systems have been examined for their ability to transfect CNS cells. Building upon our earlier use of cationic liposomes formulated from 3β-[N-(N′,N′-dimethylaminoethane)carbamoyl] cholesterol (DC-Chol) and dioleoyl-L-α-phosphatidyl-ethanolamine (DOPE), we describe studies using two cationic viral peptides, μ (mu) and Vp1, as potential enhancers for cationic liposome-mediated transfection. Mu is derived from the condensed core of the adenovirus and was selected to be a powerful nucleic acid charge neutralising and condensing agent. Vp1 derives from the polyomavirus and harbours a classical nuclear localisation signal (NLS). Vp1 proved disappointing but lipopolyplex mixtures formulated from pCMVβ plasmid, mu peptide and DC-Chol/DOPE cationic liposomes were able to transfect an undifferentiated neuronal ND7 cell line with β-galactosidase reporter gene five-fold more effectively than lipoplex mixtures prepared from pCMVβ plasmid and DC-Chol/DOPE cationic liposomes. Mu was found to give an identical enhancement to cationic liposome-mediated transfection of ND7 cells as poly-L-lysine (pLL) or protamine sulfate (PA). The enhancing effects of mu were found to be even greater (six- to 10-fold) when differentiated ND7 cells were transfected with mu-containing lipopolyplex mixtures. Differentiated ND7 cells represent a simple ex vivo-like post-mitotic CNS cell system. Successful transfection of these cells bodes well for transfection of primary neurons and CNS cells in vivo. These findings have implications for experimental and therapeutic uses of cationic liposome-mediated delivery of nucleic acids to CNS cells.

Original languageEnglish (US)
Pages (from-to)453-460
Number of pages8
JournalGene Therapy
Volume8
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • CNS
  • Gene therapy
  • Peptides
  • Post-mitotic

ASJC Scopus subject areas

  • Genetics

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    Murray, K. D., Etheridge, C. J., Shah, S. I., Matthews, D. A., Russell, W., Gurling, H. M. D., & Miller, A. D. (2001). Enhanced cationic liposome-mediated transfection using the DNA-binding peptide μ (mu) from the adenovirus core. Gene Therapy, 8(6), 453-460. https://doi.org/10.1038/sj.gt.3301401