Inex Pharmaceuticals Corporation

University of British Columbia

Yuan-Peng Zhang

Marcel B Bally

Michael J Hope

Peter Scherrer

Dorothy L Reimer

Pieter Rutter Cullis

Jeffery J Wheeler

Jeffery Jerome Wheeler

Jeffrey Jerome Wheeler

Ljiljana Kojic

Olga Ludkovski

Edward George Saravolac

Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.

Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer

Particle aggregation of lipid:nucleic acid complex particles is prevented by incorporating a non-cationic lipid into lipid:nucleic acid complex particles containing a cationic lipid and a nucleic acid polymer. The non-cationic lipid is a polyethylene glycol-based polymer.

Method of preventing aggregation of a lipid:nucleic acid complex

The present invention relates to lipid-based formulations for nucleic acid delivery to cells, methods for the preparation of such formulations and, in particular, to lipid encapsulated plasmids. The compositions are safe and practical for clinical use. In addition, the present invention provides methods for introducing nucleic acids into cells and for inhibiting tumor growth in cells using such lipid-nucleic acid formulations.

Methods for encapsulating nucleic acids in lipid bilayers

This invention relates to a novel Solvent Extraction and Direct Hydration (SEDH) method for preparing lipid-nucleic acid particles which are useful for the introduction of nucleic acids (e.g., plasmid DNA, antisense molecules, ribozymes, etc.) into cells. The lipid-nucleic acid particles prepared using the methods of the present invention have enhanced circulation characteristics and serum stability and, thus, they are extremely effective as nucleic acid delivery vehicles.

Preparation of lipid-nucleic acid particles using a solvent extraction

Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic

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.

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Vancouver, Canada

Yuan-Peng Zhang