Synthetic DNA-compacting peptides derived from human sequence enhance cationic lipid-mediated gene transfer in vitro and in vivo

Abstract

Cationic lipids can deliver genes efficiently in vitro, but are with classical DNA/lipid lipoplexes, and particularly confer generally inhibited by the presence of serum, and their the capacity to transfect in the presence of serum. This efficiency in vivo is much lower than in vitro. An attractive acquisition of serum resistance is cell type-independent, strategy is to induce strong DNA compaction by its associand observed with all four lipopolyamines tested and polyation with proteins, before addition of lipids. However the ethylenimine. Precompacting DNA with a histone H1-use of whole proteins might present both production and derived peptide enhances cationic lipid RPR 115335-immunological limitations. We have devised a system in mediated gene transfer in an in vivo model of Lewis lung which DNA is associated with short peptides derived from carcinoma. Apart from their use in peptide-DNA-lipid human histone or protamine, before the addition of a catassociation, such peptides could be useful as part of chimionic lipid or polymer. Peptides strongly associating with eric gene delivery vectors presenting a DNA-binding moi-DNA confer to such peptide-DNA-lipid particles an ety that can be easily associated with other functional enhanced in vitro transfection efficiency over that observed domains.

Increased receptor-mediated gene delivery to the liver by protamine-enhanced-asialofetuin-lipoplexes

“…It has been proposed that this peptide increases lipid-mediated gene transfection by condensing DNA into a compact structure, which promotes cellular entry and stability of DNA. 34,35 The use of this polycation could also improve the in vivo activity of lipoplexes 36,37 and has the additional advantage of being non-toxic in humans. In this study we examined whether a liver-targeted, stable gene transfer system could be constructed by combining the condensing effect of protamine and the targeting capability of AF.…”

Improvement of exogenous DNA nuclear importation by nuclear localization signal‐bearing vectors: a promising way for non‐viral gene therapy?

“…They suggested that the NLS peptides may constitute a valuable tool to improve the efficiency of transgenesis in several species. Several reports confirm the potential use of nuclear targeting peptides, which are non-covalently bound to vector DNA, to enhance the efficiency of biotechnological non-viral gene transfer applications (Malecki, 1996;Aronsohn and Hughes, 1998;Schwartz et al, 1999;Liang et al, 2000;Chan and Jans, 2001).…”

“…However, the use of whole protein might present both production and immunological limitations. Schwartz et al (1999) have devised a system in which DNA is associated with short peptides derived from human histone and protamine, before the addition of any cationic lipid or polymer. Indeed peptides strongly associated with DNA confer to such peptide-DNAlipid particles an enhanced in vitro transfection efficiency over that observed with classical DNA/lipid lipoplexes.…”

Characterisation of LMD virus-like nanoparticles self-assembled from cationic liposomes, adenovirus core peptide μ (mu) and plasmid DNA

“…A number of ternary systems have been described over the past few years, most importantly the lipid:protamine:DNA (LPD) vector systems reported by Huang and coworkers, and others. [6][7][8][9][10][11][12][13][14][15] Other ternary systems involving alternatives to protamine have also been described in the past few years including systems based around poly-L-lysine, 16,17 spermidine, 18 lipopolylysine, 19 histone proteins, 20,21 chromatin proteins, 22 human histone derived peptides, 23 oligo-L-lysine, [24][25][26] L-lysine containing synthetic peptides, 27 and a histidine/lysine (H-K) copolymer. 28 In our case, we chose to use the adenoviral core complex peptide (mu).…”