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Non-viral gene delivery: optimising in vivo stability and cell targeting

Reference	BBS/B/03645
Principal Investigator / Supervisor	Professor Alethea Tabor
Co-Investigators / Co-Supervisors	Professor Helen Hailes, Professor Stephen Hart
Institution	University College London
Department	Chemistry
Funding type	Research
Value (£)	342,217
Status	Completed
Type	Research Grant
Start date	01/07/2004
End date	31/01/2008
Duration	43 months

Abstract

Two important limitations to the success of current non-viral gene delivery methods are: the tendency of non-viral particles to aggregate in vivo; and the problem of endosomal release of the gene versus lysosomal degradation. Based on our previous studies of a ternary lipid/peptide/DNA (LID) gene delivery vector we will tackle both obstacles using structurally defined PEGylated lipids possessing endosomally cleavable PEG units, and cell-specific receptor targeted peptides with endosomally cleavable target moieties. This integrated interdisciplinary proposal will involve: synthesis of novel lipids, peptides and lipopeptides; systematic biophysical and in vitro transfection studies of the stability of the resulting vectors under different buffer and serum conditions, and structural investigations of the vectors. These will be correlated to a focused investigation of the in vivo transfection properties of the optimised vectors in a cancer neuroblastoma model.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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