Modular system for gene and protein delivery based on aav

Patent metadata

Field	Value
Publication number	US-2020407751-A1
Application number	US-201916976720-A
Country	US
Kind code	A1
Filing date	Feb 28, 2019
Priority date	Feb 28, 2018
Publication date	Dec 31, 2020
Grant date	—

Abstract

In one embodiment, the invention provides an Adeno-Associated Virus (AAV) comprising an exterior surface, which surface comprises one or more peptide tags that form a bond with a binding-partner, wherein the AAV is a live virus. In another embodiment, the invention provides a conjugate comprising at least one such AAV and at least one polypeptide comprising a first domain which is the binding-partner for the tag and a second domain, which is a bioactive polypeptide. In another embodiment, the invention provides a conjugate comprising at least one such AAV (first AAV) and at least one second AAV, which second AAV comprises a second exterior surface, which second exterior surface comprises at least one binding-partner for the tag or for a third linker molecule, wherein the at least one first AAV and the at least one second AAV are bound.

First claim

1 . An Adeno-Associated Virus (AAV) comprising an exterior surface, which surface comprises one or more peptide tags that form a bond with a binding-partner, wherein the AAV is a live virus.

2 . A conjugate comprising an AAV and at least one polypeptide, wherein said AAV comprises an exterior surface, which surface comprises one or more peptide tags that form a bond with a binding-partner, wherein said AAV is a live virus, wherein said polypeptide comprises a first domain which comprises the binding-partner for said one or more peptide tags and a second domain, which comprises a bioactive polypeptide, wherein the AAV and the polypeptide are bound.

3 . The conjugate of claim 2 , wherein the second domain comprises Cas9.

4 . A conjugate comprising at least one first AAV and at least one second AAV, wherein said first AAV comprises an exterior surface, which surface comprises one or more peptide tags that form a bond with a binding-partner, wherein said first AAV is a live virus, wherein said second AAV comprises a second exterior surface, which second exterior surface comprises at least one binding-partner for said one or more peptide tags or for a third linker molecule, wherein the at least one first AAV and the at least one second AAV are bound, and wherein the at least one second AAV is a live virus.

5 . The conjugate of claim 4 , wherein the first AAV and the second AAV within the conjugate comprise genomes comprising separate respective segments of a transgene, such that the complete transgene can be assembled upon infection of a cell with the conjugate.

6 . The conjugate of claim 4 , wherein the exterior surface of the at least one first AAV comprises at least one binding-partner for said one or more peptide tags that forms a bond with a binding-partner.

7 . The conjugate of claim 4 , wherein the second exterior surface of the at least one second AAV comprises one or more peptide tags that form a bond with a binding-partner.

8 . The conjugate of claim 4 , comprising more than one of said first AAVs.

9 . The conjugate of claim 4 , comprising more than one of said second AAVs.

10 . The conjugate of claim 4 , comprising a third linker molecule, where the third linker molecule bridges the AAVs together.

11 . The conjugate of claim 1 , wherein the bond is a covalent bond.

12 . A composition comprising (a) a cell and (b) an AAV or conjugate, wherein the cell is infected with the AAV or conjugate,
wherein said AAV comprises an exterior surface, which surface comprises one or more peptide tags that form a bond with a binding-partner, wherein said AAV is a live virus, and wherein said conjugate comprises said AAV and at least one polypeptide, wherein said polypeptide comprises a first domain which comprises the binding-partner for said one or more peptide tags and a second domain, which comprises a bioactive polypeptide, wherein said AAV and said polypeptide are bound.

13 . The composition of claim 12 , wherein said cell is in vivo.

14 . The composition of claim 12 , wherein said cell is human.

15 . The composition of claim 12 , wherein said cell is a bovine, canine, caprine, equine, feline, ovine, porcine, or primate cell.

16 . A pharmaceutical composition comprising (a) an AAV or conjugate and (b) a pharmaceutically-acceptable carrier,
wherein said AAV comprises an exterior surface, which surface comprises one or more peptide tags that form a bond with a binding-partner, wherein said AAV is a live virus, and wherein said conjugate comprises said AAV and at least one polypeptide, wherein said polypeptide comprises a first domain which comprises the binding-partner for said one or more peptide tags and a second domain, which comprises a bioactive polypeptide, wherein said AAV and said polypeptide are bound.

Assignees

• Univ Pittsburgh Commonwealth Sys Higher Education
• Univ California

Inventors

• Byrne Leah
• Ozturk Bilge Esin
• Day Timothy

Classifications

• C07K14/005

  from viruses · CPC title

• C12N15/86 Primary

  Viral vectors · CPC title

• C12N2800/40

  Systems of functionally co-operating vectors · CPC title

• C12N2750/14122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C12N2750/14121

  Viruses as such, e.g. new isolates, mutants or their genomic sequences · CPC title