Parker, A.L., Collins, L., Zhang, X. and Fabre, J.W. (2005) Exploration of peptide motifs for potent non-viral gene delivery highly selective for dividing cells. Journal of Gene Medicine, 7(12), pp. 1545-1554. (doi: 10.1002/jgm.809)
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Abstract
Background The immunogenicity of viral DNA vectors is an important problem for gene therapy. The use of peptide motifs for gene delivery would largely overcome this problem, and provide a simple, safe and powerful approach for non-viral gene therapy. Methods We explored the functional properties of two motifs: the (Lys)<sub>16</sub> motif (for binding and condensing DNA, and probably also nuclear translocation of plasmids) and the fusogenic peptide motif of influenza virus (for acid-dependent endocytic escape of peptide/DNA particles). The physical properties and gene delivery efficiencies of (Lys)<sub>16</sub>-containing peptides in combination with free fusogenic peptide were evaluated, and compared with a single composite peptide incorporating both moieties. Post-mitotic corneal endothelial cells and growth-arrested HeLa were included, so as not to neglect the question of nuclear translocation of plasmids. Results The fusogenic moiety in the composite peptide was able to adopt an alpha-helical configuration unhindered by the (Lys)<sub>16</sub> moiety, and retained acid-dependent fusogenic properties. The composite peptide gave remarkably high levels of gene delivery to dividing cell lines. However, in marked contrast to (Lys)<sub>16</sub>/DNA complexes plus free fusogenic peptide, the composite peptide was completely ineffective for gene delivery to post-mitotic and growth-arrested cells. Conclusions Attachment of the fusogenic peptide to (Lys)<sub>16</sub> appears to block (Lys)<sub>16</sub>-mediated nuclear translocation of plasmid, but not fusogenic peptide mediated endocytic escape. This strengthens the experimental basis for (Lys)<sub>16</sub>-mediated nuclear translocation of plasmids, and provides a single peptide with potent gene delivery properties, restricted to dividing cells. This property is potentially useful in experimental biology and clinical medicine.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Parker, Dr Alan |
Authors: | Parker, A.L., Collins, L., Zhang, X., and Fabre, J.W. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Journal of Gene Medicine |
Publisher: | John Wiley & Sons, Inc. |
ISSN: | 1099-498X |
ISSN (Online): | 1521-2254 |
Published Online: | 22 July 2005 |
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