Tissue-Binding Properties of a Synthetic Peptide Dna Vector Targeted to Cell Membrane Integrins

Abstract

This study defines the cooperative nature of the binding of this vector system to target cells and establishes the cell types most likely to be effectively targeted for DNA transfer.

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

“…These data are consistent with the fact that nuclear localising signals for proteins are short cationic sequences, such as the well-known PKKKRKV sequence of the SV40 large T antigen [25]. Thus the (Lys) 16 motif in our system serves two functions -firstly, to bind and condense DNA via electrostatic interactions to form vector/DNA particles, and secondly, once in the cytosol, to translocate the DNA plasmid into the nucleus.…”

“…An early study, using chloroquine for endocytic escape, demonstrated excellent gene delivery to post-mitotic corneal endothelial cells [14]. More recently, we reported that a simple system, consisting only of a (Lys) 16 peptide and a 20 amino-acid fusogenic peptide, is able to deliver genes with >95% efficiency to post-mitotic corneal endothelial cells [13]. The fact that these (Lys) 16 based systems can overcome all cellular barriers for gene delivery, including translocation into the nucleus, strongly suggests that (Lys) 16 has nuclear translocating ability for plasmid DNA.…”

“…Our group has been developing small, (Lys) 16 containing synthetic peptides as non-viral gene delivery systems [12][13][14][15][16][17][18][19][20][21][22][23]. An early study, using chloroquine for endocytic escape, demonstrated excellent gene delivery to post-mitotic corneal endothelial cells [14].…”

“…More recently, we reported that a simple system, consisting only of a (Lys) 16 peptide and a 20 amino-acid fusogenic peptide, is able to deliver genes with >95% efficiency to post-mitotic corneal endothelial cells [13]. The fact that these (Lys) 16 based systems can overcome all cellular barriers for gene delivery, including translocation into the nucleus, strongly suggests that (Lys) 16 has nuclear translocating ability for plasmid DNA. This is supported by a study evaluating nuclear translocation in digitonin-permeabilised cells [24].…”

Targeting αvβ3 and α5β1 for gene delivery to proliferating VSMCs: synergistic effect of TGF-β1

“…We have used a nonviral gene delivery system consisting of a 15-amino acid peptide derived from the venom of the American pit viper (Crotalus molossus) linked to 16 consecutive lysines, to permit electrostatic binding of DNA, as a vector (molossin vector) (6,14,24). Molossin vector contains an RGDNP motif that displays high affinities toward ␣v␤3 and ␣5␤1 integrins (as opposed to the RGDW motif present in other pit viper venoms) (22,31).…”