Gene delivery to vascular endothelium using chemical vectors: implications for cardiovascular gene therapy

Abstract

The vascular endothelium is an attractive target for gene therapy because of its accessibility and its importance in the pathophysiology of a wide range of cardiovascular conditions. In general, viral methods have been shown to be very effective at delivering genes to endothelium. The immunogenicity and pathogenicity associated with viral vectors have led increased efforts to seek alternative means of ‘ferrying’ therapeutic genes to endothelium or to decrease the short-comings of viral vectors. This paper reviews developments in non-viral technology. In addition, discussion also covers the mechanisms whereby existing chemical vectors deliver DNA to cells. Understanding the pathways of vector internalisation and intracellular traffic is important in developing strategies to improve vector technology. The authors propose that the chemical vector may represent a robust and versatile technology to ‘ferry’ therapeutic genes to vascular endothelium in order to modify the endothelial dysfunction associated with many cardiovascular diseases.

Keywords::

• chemical vectors
• endothelial cells
• gene transfer
• liposomes
• molecular conjugates
• polymers

Acknowledgements

PHT was funded by the Medical Research Council (London, UK) and the Royal College of Surgeons, Edinburgh (Edinburgh, UK) as a Clinical Research Training Fellow (2001-2004). Andrew JT George was a mentor for TH, MM and PHT. The authors acknowledge his initial involvement in drafting the manuscript and his precious suggestions.

Due to space restrictions, the authors were able to cite only a fraction of the relevant literature and apologise to any colleagues whose contributions may not be appropriately acknowledged in this review.

Notes

This box summarises the vectors utilised for gene therapy in the context of the cardiovascular system. bFGF: Basic fibroblast growth factor; PEI: Polyethylenimine; VEGF: Vascular endothelial growth factor.