Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis

Abstract

We report the results of a double-blind, placebo-controlled trial in nine cystic fibrosis (CF) subjects receiving cationic liposome complexed with a complementary DNA encoding the CF transmembrane conductance regulator (CFTR), and six CF subjects receiving only liposome to the nasal epithelium. No adverse clinical effects were seen and nasal biopsies showed no histological or immuno-histological changes. A partial restoration of the deficit between CF and non-CF subjects of 20% was seen for the response to low Cl- perfusion following CFTR cDNA administration. This was maximal around day three and had reverted to pretreatment values by day seven. In some cases the response to low Cl- was within the range for non-CF subjects. Plasmid DNA and transgene-derived RNA were detected in the majority of treated subjects. Although these data are encouraging, it is likely that transfection efficiency and the duration of expression will need to be increased for therapeutic benefit.

ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo

“…Phase I clinical trials involving synthetic molecules (DC-Chol, DMRIE) were recently difficulty of reproducing results in independent experiments, led us to evaluate whether a new compound, performed in the USA and Europe. 5,6 Preliminary results confirmed the safety of these compounds, although their ExGen 500, might be an alternative for in vitro and in vivo gene transfer to lung cells. ExGen 500 is a linear 22 kDa low gene transfer efficiency stressed the need for the development of more efficient molecules.…”

Cationic lipid-mediated transfection of cells in culture requires mitotic activity

“…[1][2][3][4][5][6] Despite these clear advantages, nonviral transfection systems result in substantially less gene expression than that observed with viral systems. Most cationic lipid/DNA-based systems are taken up efficiently though an endocytosis pathway, [7][8][9][10] but the exact mechanisms of DNA release from the endosomes and the subsequent translocation to the nucleus are not clear.…”

Factors controlling the efficiency of cationic lipid-mediated transfection in vivo via intravenous administration

“…The able, 12 some of which have been used in clinical trials for transfection activity of the new lipid formulation is equithe treatment of cancer 13,14 and cystic fibrosis. 15,16 valent to or better than the conventional cationic lipoDespite their availability, wide use in preclinical or some composition when tested in cell culture. clinical experiments in the laboratory, and extensive tests…”