Stable polyplexes based on arginine-containing oligopeptides for in vivo gene delivery
Authors:
- 19 February 2004
- journal article
- Published by Springer Nature in Gene Therapy
- Vol. 11 (5) , 457-464
Abstract
In this study, we investigated to what extent the stability and transduction capacity of polyplexed DNA can be improved by optimizing the condensing peptide sequence. We have synthesized a small library of cationic peptides, at which the lysine/arginine ratio and the cation charge were varied. All peptides were able to compact DNA, at which polyplexes of short lysine-rich sequences were considerably larger than those of elongated or arginine-rich peptides (GM102 and GM202). In addition, the arginine-rich peptides GM102 and GM202 rendered the polyplexes resistant to plasma incubation or DNase I-mediated digestion. While all peptides were found to improve the transfection efficiency in HepG2 cells, only the GM102- and GM202-derived polyplexes could be specifically targeted to HepG2 cells by incorporation of a ligand-derivatized YKAK8WK peptide. We propose that GM102 and GM202 combine the advantage of small condensing peptides to give small-sized polyplexes with the superior stability of condensing polymers, which makes GM102 and GM202 excellent candidates for future in vivo gene therapy studies.Keywords
This publication has 37 references indexed in Scilit:
- Specific systemic nonviral gene delivery to human hepatocellular carcinoma xenografts in SCID miceHepatology, 2002
- Nonviral Gene Transfer Strategies for the VasculatureMicrocirculation, 2002
- Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplexNature Biotechnology, 2000
- Optimization of Nonviral Gene Transfer of Vascular Smooth Muscle Cells in Vitro and in VivoMolecular Therapy, 2000
- Lyophilization of Cationic Lipid–protamine–DNA (LPD) ComplexesJournal of Pharmaceutical Sciences, 2000
- Non-Viral Peptide-Based Approaches to Gene DeliveryJournal of Drug Targeting, 1999
- In Vivo Disposition Characteristics of Plasmid DNA Complexed with Cationic LiposomesJournal of Drug Targeting, 1995
- Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes: toward a synthetic virus-like gene-transfer vehicle.Proceedings of the National Academy of Sciences, 1992
- Retrovirus-mediated transduction of adult hepatocytes.Proceedings of the National Academy of Sciences, 1988
- Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.Proceedings of the National Academy of Sciences, 1987