abstract |
Novel, hydrophobic lipid-nucleic acid complexes. The complexes are charge-neutralized and contain the nucleic acid in a non-condensed form. Manipulation of these complexes in either detergent-based or organic solvent-based systems leads to particle formation. Thus, the present invention also provides methods of preparing lipid-nucleic acid particles which are useful for the therapeutic delivery of nucleic acids. The particles are constructed via hydrophobic lipid-nucleic acid intermediates (or complexes). Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the nucleic acid forms a particle with lipids and is protected from degradation. The particles thus formed are suitable for use in intravenous nucleic acid transfer as they are stable in circulation, of a size required for pharmacodynamic behavior resulting in access to extravascular sites and target cell populations. |