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Exploration of peptide motifs for potent non-viral gene delivery highly selective for dividing cells

Parker, Alan L. ORCID:, Collins, Louise, Zhang, X. H. and Fabre, John 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. 10.1002/jgm.809

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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)16 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)16-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)16 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)16/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)16 appears to block (Lys)16-mediated nuclear translocation of plasmid, but not fusogenic peptide mediated endocytic escape. This strengthens the experimental basis for (Lys)16-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: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
Publisher: Wiley-Blackwell
Last Modified: 24 Oct 2022 10:08

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