Methods and compounds for controlled release of recombinant parvovirus vectors
View Patent ↗The invention uses recombinant parvoviruses, and particularly recombinant adeno-associated virus (rAAV) to deliver genes and DNA sequences for gene therapy following manipulation of the therapeutic virus for packaging and transport. The invention delivers therapeutic viral vectors via rAAV affixed to support matrixes (i.e., sutures, surgically implantable materials, grafts, and the like).
1. A surgically implantable matrix comprising a recombinant adeno-associated virus (rAAV) vector dried thereto, wherein the rAAV vector comprises a heterologous nucleic acid.
2. The surgically implantable matrix according to claim 1 , wherein the vector comprises an AAV Type 1 capsid.
3. The surgically implantable matrix according to claim 1 , wherein the vector comprises an AAV Type 2 capsid.
4. The surgically implantable matrix according to claim 1 , wherein the vector comprises an AAV Type 3 capsid.
5. The surgically implantable matrix according to claim 1 , wherein the vector comprises an AAV Type 4 capsid.
6. The surgically implantable matrix according to claim 1 , wherein the vector comprises an AAV Type 5 capsid.
7. The surgically implantable matrix according to claim 1 , wherein the vector comprises an AAV Type 6 capsid.
8. The surgically implantable matrix according to claim 1 , wherein the vector is an AAV Type 1, Type 2, Type 3, Type 4, Type 5 or Type 6 vector.
9. The surgically implantable matrix according to claim 1 , wherein the AAV vector is a hybrid AAV vector.
10. The surgically implantable matrix according to claim 1 , wherein the AAV vector is a chimeric AAV vector.
11. The surgically implantable matrix according to claim 1 , wherein the AAV vector is a targeted AAV vector.
12. The surgically implantable matrix according to claim 1 , wherein the heterologous nucleic acid encodes a polypeptide.
13. The surgically implantable matrix according to claim 12 , wherein the heterologous nucleic acid encodes factor IX, erythropoietin, superoxide dismutase, globin, leptin, thymidine kinase, catalase, tyrosine hydroxylase, a cytokine, a peptide growth factor or hormone, dystrophin, a mini-dystrophin, bone morphogenetic protein (BMP), or ornithine transcarbamylase.
14. The surgically implantable matrix according to claim 12 , wherein the heterologous nucleic acid encodes a peptide growth factor.
15. The surgically implantable matrix according to claim 12 , wherein the heterologous nucleic acid encodes a nerve growth factor.
16. The surgically implantable matrix according to claim 15 , wherein the nerve growth factor is glial cell line-derived neurotrophic factor (GDNF).
17. The surgically implantable matrix according to claim 12 , wherein the heterologous nucleic acid encodes a mini-dystrophin.
18. The surgically implantable matrix according to claim 12 , wherein the heterologous nucleic acid encodes a BMP.
19. The surgically implantable matrix according to claim 12 , wherein the heterologous nucleic acid encodes a cancer antigen or tumor antigen.
20. The surgically implantable matrix according to claim 12 , wherein the heterologous nucleic acid encodes a bacterial antigen, viral antigen, protozoan antigen, or parasite antigen.
21. The surgically implantable matrix according to claim 1 , wherein the heterologous nucleic acid encodes an antisense nucleic acid, a ribozyme, an RNA that effects spliceosome-mediated trans-splicing, an interfering RNA (RNAi), a guide RNA, or other non-translated RNA.
22. The surgically implantable matrix according to claim 1 , wherein the heterologous nucleic acid encodes an RNAi.
23. The surgically implantable matrix according to claim 1 , wherein the surgically implantable matrix comprises an implantable device, a surgical graft material, a positively-charged nylon membrane, a suture, cat gut, a tissue scaffold, or a bone graft substitute.
24. The surgically implantable matrix according to claim 1 , wherein the surgically implantable matrix comprises polytetrafluoroethylene (GORTEX®), poliglecaprone (MONOCRYL®), high density polyethylene (MARLEX®), polypropylene, polyglactin, polydiaxanone (PDS), a foam gelatin matrix, or polyethylene terephthalate (DACRON®).
25. The surgically implantable matrix according to claim 1 , wherein the surgically implantable matrix is coated.
26. A method of storing an adeno-associated virus (AAV) vector, the method comprising drying the AAV vector to a surgically implantable matrix.
27. The method of claim 26 , wherein the surgically implantable matrix having the AAV vector dried thereto is stored at room temperature.