Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor

• US 7,238,673 B2
• Filed: 09/25/2001
• Issued: 07/03/2007
• Est. Priority Date: 03/31/1989
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Nabel, Gary J., Nabel, Elizabeth G.
• Primary Examiner(s): ZARA, JANE J
• Application Number:
  US09/962,489
• Publication Number:
  US 20020034505A1
• Time in Patent Office: 2,107 Days
• Field of Search: 435/6, 435/91.1, 435/91.31, 435/455, 435/458, 435/320.1, 514/44, 536/23.1, 536/24.5
• US Class Current: 514/44.00A
• CPC Class Codes: A61B 17/22 Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for dilators A61M29/00
• CPC Class Codes: A61B 2017/22038 with a guide wire
• CPC Class Codes: A61B 2017/22054 with two balloons
• CPC Class Codes: A61B 2017/22082 after introduction of a substance
• CPC Class Codes: A61B 2017/22084 stone- or thrombus-dissolving
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• 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 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence

Abstract

A method for the direct in vivo transformation of cells in and surrounding a solid tumor is disclosed. This method is based on the site-specific delivery of proteins to solid tumors and to tissue surrounding the solid tumor by direct injection of a nucleic acid sequence. In particular, this method is directed to site-specific delivery of nucleic acids encoding major histocompatibility proteins, cytokines, and toxins to a solid tumor. This technique provides for the transfer of vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of disease.

Claims

1. A method of transfecting cells at a blood vessel wall or in tissues surrounding the blood vessel wall, comprising site specifically delivering an antisense agent into the blood vessel in an amount sufficient to transfect the cells, wherein the antisense agent is complementary to a region of a target gene expressed by the cells and wherein the antisense agent is delivered via a catheter.

2. The method of claim 1 wherein the antisense agent is delivered via balloon catheter.

3. The method of claim 1 wherein the target gene encodes a protein which induces angiogenesis.

11. The method of claim 1, wherein the antisense agent is administered as a nucleic acid/liposome complex.

12. The method of claim 1, wherein the antisense agent is contained in a vector expressing a nucleic acid sequence complementary to a region of a target gene expressed by the cells.

13. The method of claim 12, wherein the vector is a eukaryotic or viral vector.

14. The method of claim 13, wherein the viral vector is an adenoviral vector.

4. A method of delivering an antisense agent to a site at a blood vessel wall or in tissues surrounding the blood vessel wall, comprising introducing the antisense agent into the blood vessel wall or tissues surrounding the blood vessel wall via a catheter and releasing the antisense agent in an amount sufficient to transform cells of the blood vessel wall, cells in tissues surrounding the blood vessel wall or both.

5. The method of claim 4 wherein the antisense agent comprises an oligonucleotide complementary to a region of a gene encoding a protein that induces angiogenesis.

6. The method of claim 4 wherein the antisense agent is contained in a plasmid which expresses the complement of a region of a gene encoding a protein that induces angiogenesis.

7. The method of claim 5 wherein the antisense agent is complementary to a portion of the 5′

untranslated region of the gene.

8. The method of claim 5 wherein the antisense agent is complementary to a portion of the coding region of the gene.

9. The method of claim 5 where the antisense agent is complementary to a portion of the 3′

untranslated region of the gene.

10. The method of claim 4 wherein the antisense agent is delivered by a balloon.

15. The method of claim 4, wherein the antisense agent is administered as a nucleic acid/liposome complex.

16. The method of claim 4, wherein the antisense agent is contained in a vector expressing a nucleic acid sequence complementary to a region of a target gene expressed by the cells.

17. The method of claim 16, wherein the vector is a eukaryotic or viral vector.

18. The method of claim 17, wherein the viral vector is an adenoviral vector.