Ester J Kwon1, Sylvie Liong, Suzie H Pun. 1. Department of Bioengineering, University of Washington, 3720 15th Avenue NE, Seattle, Washington 98195, USA.
Abstract
HGP is a 24-amino acid peptide derived from HIV gp41 that increases vesicular escape when incorporated into gene delivery vehicles. The typical yield of HGP from solid phase peptide synthesis is low due to its length and hydrophobicity. The goal of this work was to investigate truncated sequences that maintained activity in order to improve the ease and yield of synthesis. A shortened, 15-amino acid sequence retained comparable lytic activity and the ability to interact with lipids when compared to the full length peptide. A scrambled peptide showed poor lytic activity, confirming that the activity of these endosomal escape peptides is sequence specific. Peptides were covalently attached to polyethylenimine (PEI) and used to condense plasmid DNA to form nanoparticulate carriers. When delivery efficiencies of PEI-peptide conjugates were compared in vitro, PEI modified with the truncated HGP sequence increased transgene expression over unmodified PEI and full length HGP.
HGP is a 24-amino acid n class="Chemical">peptide derived from HIV gp41 that increases vesicular escape whenpan> incorporated into genpan>e delivery vehicles. The typicn class="Chemical">al yield of HGP from solid phase peptide synthesis is low due to its length and hydrophobicity. The goal of this work was to investigate truncated sequences that maintained activity in order to improve the ease and yield of synthesis. A shortened, 15-amino acid sequence retained comparable lytic activity and the ability to interact with lipids when compared to the full length peptide. A scrambled peptide showed poor lytic activity, confirming that the activity of these endosomal escape peptides is sequence specific. Peptides were covalently attached to polyethylenimine (PEI) and used to condense plasmid DNA to form nanoparticulate carriers. When delivery efficiencies of PEI-peptide conjugates were compared in vitro, PEI modified with the truncated HGP sequence increased transgene expression over unmodified PEI and full length HGP.
Authors: Sabine Boeckle; Katharina von Gersdorff; Silke van der Piepen; Carsten Culmsee; Ernst Wagner; Manfred Ogris Journal: J Gene Med Date: 2004-10 Impact factor: 4.565
Authors: Russell N Johnson; David S H Chu; Julie Shi; Joan G Schellinger; Peter M Carlson; Suzie H Pun Journal: J Control Release Date: 2011-07-14 Impact factor: 9.776