Inex Pharmaceuticals Corporation

University of British Columbia

Jeffery J Wheeler

Marcel B Bally

Pieter Rutter Cullis

Michael J Hope

Yuan-Peng Zhang

Dorothy L Reimer

Peter Scherrer

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

Plasmid-lipid particles which are useful for transfection of cells in vitro or in vivo are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. The particles are typically 65-85 nm, fully encapsulate the plasmid and are serum-stable.

Methods for encapsulating plasmids in lipid bilayers

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.

Microemulsion compositions for the delivery of hydrophobic compounds are provided. Such compositions have a variety of uses. In one embodiment, the hydrophobic compounds are therapeutic agents including drugs. The present invention also discloses methods for in vitro and in vivo delivery of hydrophobic compounds to cells. Uses of the methods in vitro include the testing of hydrophobic compounds for cytotoxicity. Uses of the methods in vivo include diagnostic and therapeutic purposes.

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Richmond, CA, United States of America

Jeffery J Wheeler