Complexes of adenovirus with cationic molecules
AssigneeUniversity of Iowa
InventorsMichael J. Welsh, Allen J. Fasbender
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Abstract
The present invention provides noncovalent complexes of cationic molecules and adenoviral vectors containing a transgene. The complexes of the invention exhibit increased efficiency of gene transfer to a target cell relative to adenoviral vectors alone. Methods of making and using the complexes are also provided. A method of delivering cystic fibrosis transmembrane conductance regulator to a CF patient utilizing a complex of cationic molecules and adenoviral vectors containing a transgene encoding a CFTR protein is provided.
Claims17
A noncovalent complex comprising cationic lipids, or cationic polymers selected from the group consisting of poly-L-lysine, polyethyleneimine, DEAE-dextran, histone and cationic dendrimer, and adenoviral particles wherein said adenoviral particles comprise a transgene operably linked to an expression control sequence.
A method of making a noncovalent complex comprising cationic lipids, or cationic polymers selected from the group consisting of poly-L-lysine, polyethyleneimine, DEAE-dextran, histone and cationic dendrimer, and adenoviral particles wherein said adenoviral particles comprise a transgene operably linked to an expression control sequence, said method comprising mixing said cationic lipids or cationic polymers with said adenoviral particles.
A method for delivering a transgene to an airway epithelial cell comprising combining cationic lipids, or cationic polymers selected from the group consisting of poly-L-lysine, polyethyleneimine, DEAE-dextran, histone and cationic dendrimer, and adenoviral particles comprising said transgene operably linked to an expression control sequence to form a noncovalent complex, and introducing said complex into said airway epithelial cell.
The method of claim 11 wherein said cationic lipids are selected from the group consisting of DC-Chol, GL-67, GL-53, DOSPA, DOGS, DOSPER, DOTAP, DOTMA, DMRIE, .beta.AE-DMRIE DDAB, LIPOFECTIN.RTM., LIPOFECTAMINE.TM., LIPOFECTACE.TM., TRANSFECTAM.RTM., Tfx.TM.-50 and DMRIE-C.TM..
A method of providing cystic fibrosis transmembrane conductance regulator to airway epithelial cells of a cystic fibrosis patient comprising combining cationic lipids, or cationic polymers selected from the group consisting of poly-L-lysine, polyethyleneimine, DEAE-dextran histone and cationic dendrimer, with adenoviral particles containing a transgene encoding cystic fibrosis transmembrane conductance regulator, wherein said transgene is operably linked to an expression control sequence, to form a noncovalent complex, and administering said complex to the airway epithelial cells of said cystic fibrosis patient, in an amount and under conditions whereby said transgene is expressed and a functional chloride channel is produced in the airway epithelial cells of said patient.
A method for delivering a transgene to a target cell in vitro comprising combining cationic lipids, or cationic polymers selected from the group consisting of poly-L-lysine, polyethyleneimine, DEAE-dextran, histone and cationic dendrimer, and adenoviral particles comprising said transgene operably linked to an expression control sequence to form a noncovalent complex, and introducing said complex into said target cell.
Dependencies are inferred from the claim text.