IP Library Granted Patent US 12,091,435
Granted Patent B2
US 12,091,435 · App. 17/045,090 · Granted Sep 17, 2024

Antibody-evading virus vectors

Inventors: Daniel McCoy (Durham, NC); Garrett E. Berry (Durham, NC); James Kennon Smith (Durham, NC)
Assignee: Ginkgo Bioworks, Inc.
C07K14/015C07K14/005C07K14/4707C12N7/00C12N9/22C12N15/11C12N15/86A61K38/00C12N2750/14122C12N2750/14143
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Quick Facts
Patent No.
US 12,091,435
App. No.
17/045,090
Granted
Sep 17, 2024
Kind
B2
Abstract

The present disclosure provides AAV capsid proteins comprising a modification in the amino acid sequence and virus vectors comprising the modified AAV capsid protein. The disclosure also provides methods of administering the virus vectors and virus capsids of the disclosure to a cell or to a subject in vivo.

Claims (22)

1. A recombinant adeno-associated virus (AAV) capsid protein,

wherein the AAV capsid protein comprises the amino acid sequence of SEQ ID NO: 19.

2. An adeno-associated virus (AAV) vector, comprising the recombinant AAV capsid protein of claim 1 , and an encapsidated nucleic acid, wherein the encapsidated nucleic acid is encapsidated by the AAV capsid protein.

3. The AAV vector of claim 2 , wherein the encapsidated nucleic acid comprises a 5′ inverted terminal repeat (5′ ITR), a heterologous nucleic acid sequence, and a 3′ ITR.

4. The AAV vector of claim 3 , wherein the heterologous nucleic acid encodes one or more of the following proteins: cystic fibrosis transmembrane regulator protein (CFTR), dystrophin, myostatin propeptide, follistatin, activin type II soluble receptor, sarcospan, utrophin, factor VIII, factor IX, factor X, erythropoietin, angiostatin, endostatin, catalase, tyrosine hydroxylase, superoxide dismutase, leptin, low-density lipoprotein (LDL) receptor, lipoprotein lipase, ornithine transcarbamylase, β-globin, α-globin, spectrin, alpha-1-antitrypsin, adenosine deaminase, hypoxanthine guanine phosphoribosyl transferase, β-glucocerebrosidase, sphingomyelinase, lysosomal hexosaminidase A, branched-chain keto acid dehydrogenase, alpha-interferon, beta-interferon, gamma-interferon, interleukin-2, interleukin-4, granulocyte-macrophage colony stimulating factor, lymphotoxin, somatotropin, insulin, insulin-like growth factor 1 or 2, platelet derived growth factor, epidermal growth factor, fibroblast growth factor, nerve growth factor, neurotrophic factor-3 or -4, brain-derived neurotrophic factor, receptor activator of nuclear factor kappa beta (RANKL), vascular endothelial growth factor (VEGF), glial derived neurotrophic factor (GDNF), transforming growth factor-alpha or beta, lysosomal acid alpha-glucosidase, alpha-galactosidase A, tumor necrosis growth factor soluble receptor, S100 calcium binding protein A1 (S100A1), parvalbumin, adenylyl cyclase type 6, beta adrenergic receptor kinase carboxyl-terminus (bARKct), aspartoacylase, trastuzumab, galanin, neuropeptide Y, vasohibin 2, thymidine kinase, cytosine deaminase, diphtheria toxin, tumor necrosis factor, p53, retinoblastoma (Rb), Wilms' tumor 1 (Wt-1), TNF-related apoptosis-inducing ligand (TRAIL), and/or FAS-ligand.

5. The AAV vector of claim 3 , wherein the heterologous nucleic acid encodes a micro-dystrophin protein.

6. The AAV vector of claim 3 , wherein the heterologous nucleic acid encodes a gene editing molecule.

7. The AAV vector of claim 6 , wherein the gene editing molecule is a Cas9 nuclease, or a Cpf1 nuclease.

8. A method of introducing a nucleic acid molecule into a cell, comprising contacting the cell with the AAV vector of claim 2 .

9. A pharmaceutical composition, comprising the AAV vector of claim 2 and a pharmaceutically acceptable carrier.

10. A nucleic acid comprising a nucleotide sequence encoding the recombinant AAV capsid protein of claim 1 .

11. An expression vector, comprising a nucleotide sequence encoding the recombinant AAV capsid protein of claim 1 .

12. A cell, comprising the nucleic acid of claim 10 .

13. The AAV vector of claim 3 , wherein the heterologous nucleic acid sequence encodes a polypeptide.

14. The AAV vector of claim 13 , wherein the polypeptide is a therapeutic polypeptide.

15. The AAV vector of claim 13 , wherein the polypeptide is an immunogenic polypeptide.

16. The AAV vector of claim 3 , wherein the heterologous nucleic acid sequence encodes an untranslated RNA.

17. The AAV vector of claim 16 , wherein the untranslated RNA is a guide RNA.

18. The AAV vector of claim 16 , wherein the untranslated RNA is an antisense RNA, a ribozyme, or an interfering RNA.

19. A method of producing an adeno-associated virus (AAV) capsid protein, the method comprising:

a. culturing the cell of claim 12 ; and

b. collecting the AAV capsid protein from the cell.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 26, 2023
From: STRIDEBIO, INC.
To: GINKGO BIOWORKS, INC.
Reel/Frame 063443/0637 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2021
From: MCCOY, DANIEL; BERRY, GARRETT E.; SMITH, JAMES KENNON
To: STRIDEBIO, INC.
Reel/Frame 058472/0591 →
Continuity (5)
Provisional Application 62819389 · Mar 15, 2019
Provisional Application 62776793 · Dec 7, 2018
Provisional Application 62770240 · Nov 21, 2018
Provisional Application 62652103 · Apr 3, 2018
Related Publication 20210371471A1 · Dec 2, 2021