Prostate-targeting adeno-associated virus serotype vectors

Patent metadata

Field	Value
Publication number	US-11426469-B2
Application number	US-201615769953-A
Country	US
Kind code	B2
Filing date	Oct 21, 2016
Priority date	Oct 22, 2015
Publication date	Aug 30, 2022
Grant date	Aug 30, 2022

Abstract

The disclosure relates to compositions and methods for rAAV-mediated delivery of a transgene to a subject. In some embodiments, the rAAV transduces the prostate tissue of a subject. In some embodiments, the methods are useful for treatment of prostate disease (e.g., prostatitis, BPH, prostate cancer).

First claim

What is claimed is:

1. A method for delivering a transgene to prostate tissue, the method comprising:
administering to prostate tissue of a subject an effective amount of a recombinant adeno-associated virus (rAAV), wherein the rAAV comprises (i) a wild-type capsid protein comprising an amino acid sequence that is identical to any one of SEQ ID NO: 1 or 3-7, and (ii) an isolated nucleic acid comprising a promoter operably linked to a transgene, and wherein the rAAV infects cells of the prostate tissue.

2. The method of claim 1 , wherein the capsid protein consists of an amino acid sequence that is identical to any one of SEQ ID NO: 1 or 3-7.

3. The method of claim 1 , wherein the transgene encodes a gene associated with a prostate disease, optionally wherein the prostate disease is selected from prostatitis, prostate cancer, and benign prostate hyperplasia (BPH).

4. The method of claim 3 , wherein the gene encodes a gene selected from the group consisting of B-cell lymphoma 2 (BCL-2), phosphatase and tensin homolog (PTEN), solute carrier family 39 member 1 (SLC39A1), breast cancer type 1 (BRCA1), breast cancer type 2 (BRCA2), hereditary prostate cancer-1 (HPC1), Runt-related transcription factor 2 (RUNX2), chloride channel accessory 2 (CLCA2), yes-associated protein 1 (YAP1), mammary serine protease inhibitor (MASPIN), LL37, cyclin dependent kinase inhibitor 1B (CDKN1B), androgen receptor (AR), NKX3.1, caspase 9 (CASP9), forkhead in rhabdomyosarcoma (FKHR), glycogen synthase kinase 3 (GSK3), mouse double minute 2 homolog (MDM2), extracellular signal-regulated kinase 1/2 (ERK1/2), prostate-specific antigen (PSA), cyclin D1 (CCND1), aldolase A (ALDOA), SRY-related HMG-box 4 (Sox4), CD44, and miR34a.

5. The method of claim 1 , wherein the administration occurs by injection, optionally wherein:
i) the injection is not intraperitoneal (i.p.) injection; or
ii) the injection is intraprostate injection.

6. The method of claim 1 , wherein the administration results in transduction of a prostate cell type selected from the group consisting of luminal prostate cells, basal prostate cells, and stromal prostate cells, optionally at least two prostate cell types.

7. The method of claim 1 , wherein the rAAV further comprises two AAV inverted terminal repeats (ITRs), wherein the ITRs flank the transgene.

8. The method of claim 1 , wherein the capsid protein consists of an amino acid sequence that is identical to any one of SEQ ID NO: 1 or 3-7.

9. The method of claim 1 , wherein the capsid protein comprises an amino acid sequence that is identical to SEQ ID NO: 3 or 4.

10. A method for treating a prostate disease, the method comprising: administering to the prostate tissue of a subject having or suspected of having a prostate disease an effective amount of rAAV, wherein the rAAV comprises (i) a wild-type capsid protein comprising an amino acid sequence that is identical to any one of SEQ ID NO: 1 or 3-7, and (ii) an isolated nucleic acid comprising a promoter operably linked to a transgene, and wherein the rAAV infects cells of the prostate tissue.

11. The method of claim 10 , wherein the capsid protein consists of an amino acid sequence that is identical to any one of SEQ ID NO: 1 or 3-7.

12. The method of claim 10 , wherein the transgene encodes a gene associated with a prostate disease, optionally wherein the prostate disease is selected from prostatitis, prostate cancer, and benign prostate hyperplasia (BPH).

13. The method of claim 12 , wherein the gene encodes a gene selected from the group consisting of B-cell lymphoma 2 (BCL-2), phosphatase and tensin homolog (PTEN), solute carrier family 39 member 1 (SLC39A1), breast cancer type 1 (BRCA1), breast cancer type 2 (BRCA2), hereditary prostate cancer-1 (HPC1), Runt-related transcription factor 2 (RUNX2), chloride channel accessory 2 (CLCA2), yes-associated protein 1 (YAP1), mammary serine protease inhibitor (MASPIN), LL37, cyclin dependent kinase inhibitor 1B (CDKN1B), androgen receptor (AR), NKX3.1, caspase 9 (CASP9), forkhead in rhabdomyosarcoma (FKHR), glycogen synthase kinase 3 (GSK3), mouse double minute 2 homolog (MDM2), extracellular signal-regulated kinase 1/2 (ERK1/2), prostate-specific antigen (PSA), cyclin D1 (CCND1), aldolase A (ALDO), SRY-related HMG-box 4 (Sox4), CD44, and miR34a.

14. The method of claim 10 , wherein the administration occurs by injection, optionally wherein:
i) the injection is not intraperitoneal (i.p.); or
ii) the injection is intraprostate injection.

15. The method of claim 10 , wherein the rAAV further comprises two AAV inverted terminal repeats (ITRs), wherein the ITRs flank the transgene.

16. The method of claim 10 , wherein the capsid protein comprises an amino acid sequence that is identical to SEQ ID NO: 3 or 4.

17. A method for treating a prostate disease, the method comprising: administering to a subject having or suspected of having a prostate disease an effective amount of a recombinant adeno-associated virus (rAAV) comprising a wild-type capsid protein comprising an amino acid sequence that is identical to any one of SEQ ID NO: 1 or 3-7 and a promoter operably linked to a transgene, wherein the transgene encodes miR34a, and wherein the rAAV infects cells of prostate tissue.

18. The method of claim 17 , wherein the transgene:
i) comprises the sequence set forth in SEQ ID NO.: 15 or 16; or
ii) is flanked by adeno-associated virus inverted terminal repeats (AAV ITRs).

19. The method of claim 17 , wherein the administration occurs by injection, optionally wherein:
i) the injection is not intraperitoneal (i.p.) injection; or
ii) the injection is intraprostate injection.

20. The method of claim 17 , wherein the capsid protein comprises an amino acid sequence that is identical to SEQ ID NO: 3 or 4.

Assignees

• Univ Massachusetts

Inventors

• Gao Guangping
• Ai Jianzhong
• Li Hong
• Wei Qiang

Classifications

• C07K14/005 Primary

  from viruses · CPC title

• C12N2750/10041

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

• C07K14/47

  from mammals · CPC title

• C07K14/075

  Adenoviridae · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title