Receptor-targeted nanocomplexes optimized for gene transfer to primary vascular cells and explant cultures of rabbit aorta

Molecular Therapy : the Journal of the American Society of Gene Therapy
Scott A IrvineS L Hart

Abstract

We have developed new, synthetic vector formulations that display high efficiency of gene transfer to vascular cells and tissues. The formulations comprise cationic liposomes and cationic, receptor-targeting peptides that self assemble on mixing with plasmid DNA into receptor-targeted nanocomplexes (RTNs). One such RTN formulation was optimal for transfection of primary smooth muscle cells (LYD-1), while a second was optimal for transfection of rabbit aortic explants (LYD-2). In both RTNs, the peptide was a 16-lysine motif linked to the targeting sequence CYGLPHKFCG via a short spacer sequence. The major difference between LYD-1 and LYD-2 lay in the cationic lipid component, where LYD-1 contained ditetradecyl trimethyl ammonium (DTDTMA), an unsaturated, cationic lipid with a 14-carbon alkyl tail, whereas LYD-2 contained 2,3-dioleyloxypropyl-1-trimethyl ammonium chloride (DOTMA), a cationic lipid with an 18-carbon unsaturated alkyl tail. LYD-2 transfections of aortic explants were effective with incubations performed at room temperature for as little as 30 minutes, with either saline or glucose-based solutions. Transgene expression in the explants peaked at 5 days and persisted for 14 days. The kinetics of transfected gene expre...Continue Reading

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Citations

Feb 4, 2010·Cell Biology and Toxicology·Stephen L Hart
Dec 5, 2013·Chemical Reviews·Bethany Powell Gray, Kathlynn C Brown
Aug 6, 2011·Molecular Pharmaceutics·Laila KudsiovaM Jayne Lawrence
Jul 31, 2009·Chemical Communications : Chem Comm·Santanu Bhattacharya, Avinash Bajaj
Jul 12, 2011·Cardiovascular Research·Paul D Williams, Paul A Kingston
Aug 7, 2009·Journal of Biomechanical Engineering·Todd O PangburnEfrosini Kokkoli
Jun 1, 2011·Biomaterials·Aristides D TagalakisStephen L Hart
Nov 26, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Aristides D TagalakisStephen L Hart
Jul 18, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Michele J WriterStephen L Hart
Jun 19, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mehdi RezaeeBizhan Malaekeh-Nikouei
Feb 1, 2010·Viruses·Paul D WilliamsPaul A Kingston
Mar 6, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Stephanie M GrosseStephen L Hart
Jan 24, 2013·Biomacromolecules·Aristides D TagalakisStephen L Hart

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