Method of in vivo delivery of functioning foreign genes

• US 5,676,954 A
• Filed: 05/08/1995
• Issued: 10/14/1997
• Est. Priority Date: 11/03/1989
• Status: Expired due to Term

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Brigham, Kenneth L.
• Primary Examiner(s): Ziska, Suzanne E.
• Application Number:
  US08/437,213
• Time in Patent Office: 890 Days
• Field of Search: 424/450
• US Class Current: 424/450
• CPC Class Codes: A61K 47/6911 the form being a liposome
• 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

Abstract

A method of expressing a foreign gene in cells of a mammalian organ in vivo includes the step of injecting genetic material capable of inducing desired gene products into a mammal. The genetic material is complexed to cationic liposome carriers. The genetic material is lipofected into cells of the mammalian organ. Gene expression and cellular function of the genetic material are activated to produce the desired foreign products in the cells of the organ.

Claims

1. A method of expressing a gene predominantly in a target organ in a mammal, comprising the step of:

administering by injection a nucleic acid liposome complex capable of functionally expressing said gene to said mammal at a site whereby said target organ is the first organ having a capillary bed proximal to the site of administration,

wherein said nucleic acid is complexed by ionic interaction to cationic liposomes that effect delivery of said gene predominantly to said target organ and transfect said gene into a cell in said target organ, and

wherein said gene is predominantly expressed in said target organ.

2. The method of claim 1, wherein said target organ is the kidney and said administering step comprises injecting said nucleic acid liposome complex into blood afferent to the kidney.

3. The method of claim 1, wherein said target organ is the lungs and said administering step comprises administering said nucleic acid liposome complex into the trachea by aerosol administration.

4. The method of claim 1, wherein said target organ is the lungs and said administration step comprises injecting said nucleic acid liposome complex intravenously into the blood afferent to the lungs.

5. The method of claim 1, further comprising activating transient expression of the gene by administering an activator.

6. The method of claim 5, wherein the expression of said gene is controlled by a zinc-activated promoter and said activator is zinc.

7. The method of claim 6, wherein said coding region codes for human growth hormone.

8. The method of claim 6, wherein said zinc is administered by ingestion.

9. The method of claim 1, wherein said cationic liposome has the transfection characteristics of N- 1-(2,3-dioleyloxy)propyl!-N,N,N-trimethylammonium chloride.

10. A method of expressing a gene predominantly in the lungs in a mammal comprising the step of:

administering by inhalation a plasmid capable of functionally expressing said gene to said mammal,

wherein said plasmid is complexed by ionic interaction to cationic liposomes that effect delivery of said gene predominantly to said lungs and transfects said gene into a cell in said lungs, and

wherein said gene is predominantly expressed in said lungs.

11. The method of claim 10, further comprising activating transient expression of said gene by administering an activator.

12. The method of claim 11, wherein the expression of said gene is controlled by a zinc-activated promoter and said activator is zinc.

13. The method of claim 12, wherein said coding region codes for human growth hormone.

14. The method of claim 12, wherein said zinc is administered by ingestion.

15. The method of claim 12, wherein said cationic liposome has the transfection characteristics of N- 1-(2,3-dioleyloxy)propyl!-N,N,N-trimethylammonium chloride.

16. A method of delivering a nucleic acid liposome complex predominantly to a target organ in a mammal, comprising the step of administering said nucleic acid liposome complex to said mammal by injection at a site whereby said target organ is the first organ having a capillary bed proximal to the site of administration,

wherein said nucleic acid is complexed by ionic interaction to cationic liposomes that effect delivery of said nucleic acid predominantly to said target organ and transfect said nucleic acid into a cell in said target organ.

17. The method of claim 16, wherein said target organ is the kidney and said step of administering comprises injecting said nucleic acid liposome complex into the blood afferent to the kidney.

18. The method of claim 16, wherein said target organ is the lungs and said step of administering comprises administering said nucleic acid liposome complex into the trachea by aerosol administration.

19. The method of claim 16, wherein said target organ is the lungs and administration step comprises injecting the nucleic acid liposome complex intravenously into the blood afferent to the lungs.

20. The method of claim 16, wherein said cationic liposome has the transfection characteristics of N- 1-(2,3-dioleyloxy)propyl!-N,N,N-trimethylammonium chloride.

21. A method of delivering a nucleic acid predominantly to the lungs in a mammal, comprising the step of administering said nucleic acid by inhalation,

wherein said nucleic acid is complexed by ionic interaction to one or more cationic liposomes that deliver said nucleic acid predominantly to said lungs and transfect said nucleic acid into a cell in said lungs.