Parker, A.L., Eckley, L., Singh, S., Preece, J.A., Collins, L. and Fabre, J.W. (2007) (LYS)16-based reducible polycations provide stable polyplexes with anionic fusogenic peptides and efficient gene delivery to post mitotic cells. Biochimica et Biophysica Acta: General Subjects, 1770(9), pp. 1331-1337. (doi: 10.1016/j.bbagen.2007.06.009)
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Abstract
Extracellular stability, endocytic escape, intracellular DNA release and nuclear translocation of DNA are all critical properties of non-viral vector/DNA particles. We have evaluated a (Lys)<sub>16</sub>-based linear, reducible polycation (RPC) in combination with an acid-dependent, anionic fusogenic peptide for gene delivery to dividing and post-mitotic cells. The RPC was formed from Cys(Lys)<sub>16</sub>Cys monomers. Molecular weight was 24,000 Da, corresponding to an average of 10.5 peptide monomers per RPC. Non-reducible polylysine (PLL) (27,000 Da) and monomeric (Lys)<sub>16</sub> peptide were evaluated for comparison. (Lys)<sub>16</sub>/DNA particles were disrupted at fusogenic peptide concentrations well below those used for gene delivery. By contrast, RPC/DNA an PLL/DNA particles were stable in the presence of high concentrations of the anionic peptide. Addition of 10% serum virtually abolished the transfection ability of (Lys)<sub>16</sub>/DNA/fusogenic peptide particles, but had little effect on RPC/DNA/fusogenic peptide particles. RPC/DNA/fusogenic peptide particles were highly effective for gene delivery to both cell lines and post-mitotic corneal endothelium. PLL/DNA/fusogenic peptide particles were moderately effective on cell lines, but gave no gene delivery with corneal endothelial cells. We conclude that (Lys)<sub>16</sub>-based RPC/DNA/fusogenic peptide particles provide a gene delivery system which is potentially stable in the extracellular environment and, on reductive depolymerisation, can release DNA plasmids for nuclear translocation.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Parker, Dr Alan |
| Authors: | Parker, A.L., Eckley, L., Singh, S., Preece, J.A., Collins, L., and Fabre, J.W. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Biochimica et Biophysica Acta: General Subjects |
| Publisher: | Elsevier BV |
| ISSN: | 0304-4165 |
| ISSN (Online): | 1872-8006 |
| Published Online: | 30 June 2007 |
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