Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis

Liposomes enhance delivery and expression of an RGD-oligolysine gene transfer vector in human tracheal cells

“…In addition, cationic liposomes have been shown not to provoke adverse events in cystic fibrosis patients and to bring about a level of gene transfer comparable to that reported for adenoviral vectors. 8 The results to date indicate that cationic liposomes coupled with integrin-mediated gene delivery enhance the transfection efficiency of the RGD vector probably by improving the efficiency of uptake of the complexes through a receptor-mediated mechanism and through protection of the DNA by lipofectamine and the peptide. This nonviral vector system is a first step towards development of cell-specific targeting of the airway for gene therapy of cystic fibrosis.…”

“…Cationic liposomes bind DNA by means of ionic interactions and facilitate DNA delivery by fusion with the plasma membrane, 3 and/or endocytosis. [4][5][6][7] Such vectors are easy to prepare and have limited toxicity, 8 but achieve relatively low transfection levels. Receptor-targeting DNA delivery constructs consist mainly of a receptor-binding ligand, for example transferrin or asialo-orosomucoid, conjugated to a DNA-bind-ing moiety, usually high molecular weight oligo-l-lysine (for review see Refs 9 and 10).…”

The extra- and intracellular barriers to lipid and adenovirus-mediated pulmonary gene transfer in native sheep airway epithelium

“…The two most widely used gene transfer systems are cationic lipids and adenoviruses, with both assessed in phase I studies of nasal and pulmonary delivery. [1][2][3][4][5][6][7][8] Results have been encouraging, though only limited correction of the CF bioelectric defect has been observed. With respect to the extent of gene transfer needed, a present best estimate might be approximately 5% of normal cystic fibrosis transmembrane conductance regulator (CFTR) mRNA levels within every cell, 9 complete correction of the chloride defect in approximately 5% of cells within the airway epithelium, 10 or likely some combination of the two.…”

Gene therapy for cystic fibrosis: a psychosocial study of trial participants

“…We have described elsewhere pre-clinical studies towards, 2 and clinical laboratory results of, 3 a phase I safety study of a single application of gene therapy in the form of DNA-liposomes to the nose of CF patients. The trial was double-blind, placebo-controlled with a 2-week run-in period for observation and pre-administration tests and a 4-week post-administration period for evaluation.…”