Delivery of gene therapy treatments

Patent metadata

Field	Value
Publication number	US-12397066-B2
Application number	US-202217859470-A
Country	US
Kind code	B2
Filing date	Jul 7, 2022
Priority date	May 3, 2012
Publication date	Aug 26, 2025
Grant date	Aug 26, 2025

Abstract

The present invention provides methods and materials useful delivering liquids, including liquids comprising nucleic acid molecules into cells. In particular, the present invention provides methods for delivering saline solution, exogenous compositions, and isolated vectors to kidney cells, using the renal vein as a guide and under hydrodynamic pressure. The delivery methods and materials herein are useful to research, prognose, ameliorate symptoms of kidney injury, and treat kidney pathologies.

First claim

What is claimed is:

1. A method of delivering a gene therapy treatment for a chronic kidney disease, the method comprising:
occluding the renal vein to a kidney having the chronic kidney disease;
administering a retrograde hydrodynamic injection of a therapeutic fluid into the occluded renal vein at a site between the occlusion and the kidney, the retrograde hydrodynamic injection increasing the renal venous pressure during the injection, the therapeutic fluid comprising a nucleic acid molecule;
waiting, after the retrograde hydrodynamic injection, for a decrease in the renal venous pressure before unoccluding the renal vein; and
unoccluding the renal vein.

2. The method of claim 1 , wherein the nucleic acid molecule is encoded by a vector.

3. The method of claim 2 , wherein the vector is a viral vector.

4. The method of claim 1 , wherein the nucleic acid molecule is selected from the group consisting of: DNA; RNA; cDNA; synthetic DNA; plasmid; and artificial chromosome.

5. The method of claim 1 , wherein the chronic kidney disease includes: Alport syndrome; apoll mutations; Bartter syndrome; diabetes and diabetic kidney disease; diabetes insipidus; Fabry's disease; Oculo-cerebral-renal syndrome, Gitelman syndrome; Goodpasture syndrome; hyperaldosteronism; hyponatremia (low blood sodium); Dent's disease, hyperoxaluria; IgA nephropathy; oxalate kidney stones; Liddle syndrome; medullary cystic kidney disease; medullary sponge kidney; metabolic acidosis due to Fanconi's syndrome; polycystic kidney disease; renal tubular acidosis; thin basement membrane disease, benign familial hematuria; tuberous sclerosis; tubule-interstitial kidney disease; or Finnish nephropathy.

6. The method of claim 1 , wherein the chronic kidney disease is polycystic kidney disease.

7. The method of claim 1 , wherein the chronic kidney disease is diabetic kidney disease.

8. A method of delivering a gene therapy treatment for a chronic kidney disease, the method comprising:
occluding the renal vein to a kidney having the chronic kidney disease;
administering a retrograde hydrodynamic injection of a therapeutic fluid into the occluded renal vein at a site between the occlusion and the kidney, the retrograde hydrodynamic injection increasing the renal venous pressure during the injection, the therapeutic fluid comprising a nucleic acid molecule encoded by a vector;
waiting, after the retrograde hydrodynamic injection, for a decrease in the renal venous pressure before unoccluding the renal vein; and
unoccluding the renal vein.

9. The method of claim 8 , wherein the time between occluding and unoccluding the renal vein is about three minutes or less.

10. The method of claim 8 , wherein the therapeutic fluid is administered into the occluded renal vein for a length of time that is within a range of about 1 second to about 60 seconds.

11. The method of claim 8 , wherein the retrograde hydrodynamic injection is administered for a length of time that is within a range of five seconds to 60 seconds.

12. The method of claim 8 , wherein the nucleic acid molecule reaches the lumen of a kidney tubule due to the retrograde hydrodynamic injection.

13. A method of delivering a gene therapy treatment for a chronic kidney disease, the method comprising:
occluding the renal vein to a kidney having the chronic kidney disease;
administering a retrograde hydrodynamic injection of a therapeutic fluid into the occluded renal vein at a site between the occlusion and the kidney, the retrograde hydrodynamic injection increasing the renal venous pressure during the injection, the therapeutic fluid comprising a nucleic acid molecule;
waiting, after the retrograde hydrodynamic injection, for a decrease in the renal venous pressure before unoccluding the renal vein; and
unoccluding the renal vein.

14. The method of claim 13 , wherein the nucleic acid molecule is encoded by a vector, and the vector is a viral vector.

15. The method of claim 13 , wherein the nucleic acid molecule is selected from the group consisting of: DNA; RNA; cDNA; and synthetic DNA.

16. The method of claim 13 , wherein the time between occluding and unoccluding the renal vein is about three minutes or less.

17. The method of claim 13 , wherein the therapeutic fluid is administered into the occluded renal vein for a length of time that is within a range of about 1 second to about 60 seconds.

18. The method of claim 13 , wherein the retrograde hydrodynamic injection is administered for a length of time that is within a range of five seconds to 60 seconds.

19. The method of claim 13 , wherein the macromolecule reaches the lumen of a kidney tubule due to the retrograde hydrodynamic injection.

20. The method of claim 1 , wherein the nucleic acid molecule is encoded by a plasmid, and wherein the plasmid is naked, encapsulated into microspheres, or encapsulated into liposomes.

Assignees

• Univ Indiana Res & Tech Corp
• Us Gov Veterans Affairs

Inventors

• Bacallao Robert
• Atkinson Simon
• Rhodes George J
• Corridon Peter

Classifications

• C12Y208/02

  Sulfotransferases (2.8.2) · CPC title

• C12Y101/01042

  Isocitrate dehydrogenase (NADP+) (1.1.1.42) · CPC title

• C12N2710/10041

  Use of virus, viral particle or viral elements as a vector · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61K48/0058

  Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct · CPC title