Systemic administration of cationic phosphonolipids/DNA complexes and the relationship between formulation and lung transfection efficiency.

Performances of cationic lipid formulations for intravenous gene delivery to mouse lungs have been previously reported. We report in this study that cationic phosphonolipids, when appropriately formulated, can be good synthetic vectors for gene delivery to lung after intravenous administration. One of our reagents, GLB43, was capable of mediating a 500-fold higher expression in the lungs of mice than could be obtained with free pDNA alone (P=0.

Cationic phosphonolipids as nonviral gene transfer agents in the lungs of mice.

With the aim of developing new gene transfer tools for treating CF with gene therapy, we have synthesized a novel family of molecules named cationic phosphonolipids. The most efficient among them were selected by in vitro screening to compare their activities in vivo in mouse lungs. We used a reporter gene whose activity was measured cytofluorimetrically (FACS-Gal assay) and by means of a chemiluminescence technique.

Transgene expression kinetics after transfection with cationic phosphonolipids in hematopoietic non adherent cells.

Cationic lipids are considered to be capable of efficiently and safely mediating DNA transfer into cells, although expression is transient. A new family of cationic lipids, called phosphonolipids, has been developed, with the relationship between the hydrophobic domain of the lipid molecules and the significant enhancement of transduction efficiency in a non-adherent cell line characterised in the present study. The kinetics of transfection efficiency were also investigated.

Cationic phosphonolipids as non viral vectors for DNA transfection in hematopoietic cell lines and CD34+ cells.

The ability to transfer genes into a hematopoietic stem cell and to achieve regulation of their expression in lymphoid or myeloid lineages should open many new therapeutic opportunities. Besides gene transfer mediated by virus vectors like retrovirus or adenovirus, non viral systems have the theoretical advantage of being safe and easy to manage. We developed a new family of cationic lipids called phosphonolipids, synthesized 24 new molecules, and then in a first step we tested their potential to transfer genes in human hematopoietic cell lines (K562 and TF1).