Induction of a protective immune response in a mammal by injecting a DNA sequence

• US 5,589,466 A
• Filed: 01/26/1995
• Issued: 12/31/1996
• Est. Priority Date: 03/21/1989
• Status: Expired due to Term

• Current Assignee: Vical, Inc. (Fresh Tracks Therapeutics, Inc.), Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Vical, Inc. (Fresh Tracks Therapeutics, Inc.), Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Carson, Dennis A., Wolff, Jon A., Felgner, Philip L., Rhodes, Gary H., Malone, Robert W.
• Primary Examiner(s): Crouch, Deborah
• Application Number:
  US08/380,131
• Time in Patent Office: 705 Days
• Field of Search: 514/44, 935/53, 935/55, 935/60, 935/65
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/61 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 9/0069 acting on single donors with incorporation of molecular oxygen, i.e. oxygenases (1.13)
• CPC Class Codes: C12N 9/1033 Chloramphenicol O-acetyltransferase (2.3.1.28)
• CPC Class Codes: C12N 9/1247 DNA-directed RNA polymerase (2.7.7.6)
• CPC Class Codes: C12N 9/78 acting on carbon to nitrogen bonds other than peptide bonds (3.5)
• CPC Class Codes: C12Y 113/12007 Photinus-luciferin 4-monooxygenase (ATP-hydrolysing) (1.13.12.7), i.e. firefly-luciferase

Abstract

A method for delivering an isolated polynucleotide such as DNA or RNA, to the interior of a cell in a mammal comprising the injection of an isolated polynucleotide into a muscle of the mammal where the polynucleotide is taken up by the cells of the muscle and exerts a therapeutic effect on the mammal. The method can be used to deliver a therapeutic polypeptide to the cells of the mammal, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the mammal or to provide transitory gene therapy.

Claims

1. A process for inducing a protective immune response in a mammal, comprising:

injecting into muscle or skin of said mammal a construct comprising a noninfectious, nonintegrating DNA sequence encoding an immunogen linked to a promoter sequence which can control the expression of said DNA sequence in said mammal, in an amount sufficient that uptake of said construct occurs, and sufficient expression results, to induce said protective immune response,

wherein said construct is free from association with transfection-facilitating viral particles, liposomal formulations or charged lipids.

3. The process of any of claims 1 or 2 wherein said injecting is into muscle.

4. The process of any of claims 1 or 2 wherein said injecting is into skin.

5. The process of any of claims 1 or 2 wherein said mammal is a human.

6. The process of any of claims 1 or 2 wherein said uptake is into said muscle or skin.

7. The process of any of claims 1 or 2 wherein said construct is further free from transfection facilitating calcium phosphate.

8. The process of any of claims 1 or 2 wherein said construct is further free from any transfection facilitating material.

9. The process of any of claims 1 or 2 wherein said immunogen is a viral protein.

11. The process of claim 1 wherein said protective immune response is preventative.

2. A process for providing a mammal with an immunogen, and thereby generating desired antibodies in said mammal due to the action of the immune system of said mammal on said immunogen, comprising:

injecting into muscle or skin of said mammal a construct comprising a noninfectious, nonintegrating DNA sequence encoding said immunogen linked to a promoter sequence which can control the expression of said DNA sequence in said mammal in an amount sufficient that uptake of said construct occurs, and sufficient expression results, to generate said desired antibodies,

wherein said construct is free from association with transfection-facilitating viral particles, liposomal formulations or charged lipids.

10. The process of claim 2 wherein said immunogen is a viral protein from HIV, Hepatitis or herpes virus.