title: Gene delivery using ternary lipopolyplexes incorporating branched cationic peptides: the role of Peptide sequence and branching.
abstract: Cationic peptide sequences, whether linear, branched, or dendritic, are widely used to condense and protect DNA in both polyplex and lipopolyplex gene delivery vectors. How these peptides behave within these particles and the consequences this has on transfection efficiency remain poorly understood. We have compared, in parallel, a complete series of cationic peptides, both branched and linear, coformulated with plasmid DNA to give polyplexes, or with plasmid DNA and the cationic lipid, DOTMA, mixed with 50% of the neutral helper lipid, DOPE, to give lipopolyplexes, and correlated the transfection efficiencies of these complexes to their biophysical properties. Lipopolyplexes formulated from branched Arg-rich peptides, or linear Lys-rich peptides, show the best transfection efficiencies in an alveolar epithelial cell line, with His-rich peptides being relatively ineffective. The majority of the biophysical studies (circular dichroism, dynamic light scattering, zeta potential, small angle neutron scattering, and gel band shift assay) indicated that all of the formulations were similar in size, surface charge, and lipid bilayer structure, and longer cationic sequences, in general, gave better transfection efficiencies. Whereas lipopolyplexes formulated from branched Arg-containing peptides were more effective than those formulated from linear Arg-containing sequences, the reverse was true for Lys-containing sequences, which may be related to differences in DNA condensation between Arg-rich and Lys-rich peptides observed in the CD studies.
authors.affiliation: Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London WC1H 0AJ, UK.
authors.forename: Katharina
authors.initials: K
authors.lastname: Welser
authors.forename: Frederick
authors.initials: F
authors.lastname: Campbell
authors.forename: Laila
authors.initials: L
authors.lastname: Kudsiova
authors.forename: Atefeh
authors.initials: A
authors.lastname: Mohammadi
authors.forename: Natalie
authors.initials: N
authors.lastname: Dawson
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hart
authors.forename: David J
authors.initials: DJ
authors.lastname: Barlow
authors.forename: Helen C
authors.initials: HC
authors.lastname: Hailes
authors.forename: M Jayne
authors.initials: MJ
authors.lastname: Lawrence
authors.forename: Alethea B
authors.initials: AB
authors.lastname: Tabor
mesh_terms: D002412:Cations / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002942:Circular Dichroism / Q000379:methods; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D002412:Cations; D008055:Lipids; D010455:Peptides; D004247:DNA