Adenoviral vectors for transduction of vascular tissue

Patent metadata

Field	Value
Publication number	US-9476061-B2
Application number	US-201314402791-A
Country	US
Kind code	B2
Filing date	May 23, 2013
Priority date	May 24, 2012
Publication date	Oct 25, 2016
Grant date	Oct 25, 2016

Abstract

The invention relates to the field of gene transfer, and in particular to the use of adenoviral vectors of serotype Ad49 for gene delivery to vascular tissue.

First claim

The invention claimed is:

1. A method of gene delivery or gene transfer to a vascular cell or tissue comprising contacting said vascular cell or tissue with an adenoviral gene delivery vehicle, wherein the adenoviral gene delivery vehicle comprises an Ad49 hexon protein, an Ad49 penton protein, an Ad49 fiber protein, and a nucleic acid payload comprising a heterologous gene, thereby providing a genetically modified cell or tissue.

2. The method according to claim 1 , wherein the method is performed in vitro or ex vitro.

3. The method according to claim 2 , wherein the genetically modified vascular cell or tissue is intended for introduction to a subject.

4. The method according to claim 1 further comprising introducing the genetically modified cell or tissue into a subject.

5. The method according to claim 1 , wherein the vascular cell or tissue comprises a length of blood vessel.

6. The method according to claim 5 , wherein the length of blood vessel is derived from saphenous vein, internal mammary artery, gastroepiploic artery, or inferior epigastric artery.

7. The method according to claim 4 , wherein the gene transfer or gene delivery is performed for modulation of angiogenesis or vasculogenesis, prophylaxis or treatment of peripheral vascular disease, prophylaxis or treatment of restenosis, prophylaxis or treatment of complications resulting from vascular surgery, prophylaxis or treatment of vein graft failure, modulation of vascular cell proliferation, modulation of vascular cell apoptosis, modulation of vascular cell migration, or prophylaxis or treatment of atheroma formation, atherosclerosis or vascular occlusion.

8. The method according to claim 1 , wherein the adenoviral gene delivery vehicle is not replication-competent.

9. The method according to claim 1 , wherein the nucleic acid payload lacks one or more functional adenoviral genes from the E1, E2, E3 or E4 regions.

10. The method according to claim 9 , wherein the nucleic acid payload contains no functional adenoviral genes.

11. The method according to claim 1 , wherein the nucleic acid payload comprises a heterologous gene encoding a cytokine, antibody, immunostimulatory factor, anti-angiogenic factor, angiogenic factor, anti-inflammatory protein, regulator of vascular remodelling, pro-apoptotic factor for vascular cells, or metalloprotease inhibitor.

12. The method according to claim 1 , wherein the nucleic acid payload comprises a heterologous gene encoding a nucleic acid capable of hybridising to mRNA or DNA of a target gene or a nucleic acid capable of inhibiting expression of a target gene by co-suppression.

13. A method of gene delivery or gene transfer to a human smooth muscle cell (hSMC) comprising contacting the hSMC with an adenoviral gene delivery vehicle, wherein the adenoviral gene delivery vehicle comprises an Ad49 hexon protein, an Ad49 penton protein, an Ad49 fiber protein, and a nucleic acid payload comprising a heterologous gene, thereby providing a genetically modified hSMC.

14. The method according to claim 13 , wherein the hSMC is obtained from a saphenous vein.

15. The method according to claim 13 , further comprising introducing the genetically modified hSMC into a subject.

Assignees

• Crucell Holland Bv
• Janssen Vaccines & Prevention Bv

Inventors

• Baker Andrew
• Nicklin Stuart
• Parker Alan

Classifications

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/08

  Vasodilators for multiple indications · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title