Granted Patent
B2
US 12,467,063 · App. 17/193,030 · Granted Nov 11, 2025
Recombinant AAV vectors useful for reducing immunity against transgene products
Inventors:
Guangping Gao (Worcester, MA); Phillip D. Zamore (Worcester, MA); Shaoyong Li (Worcester, MA)
Assignee:
University of Massachusetts
C12N15/86A61K38/1709A61K38/28A61K38/446A61K38/4846A61K38/51A61K48/0008C07K16/1003C07K16/22C07K16/2875C07K16/2887C07K16/32C12N7/00C12N15/113C12N15/117C12N2310/141C12N2310/17C12N2320/30C12N2330/51C12N2710/10322C12N2710/10332C12N2750/14143C12N2760/00042C12N2830/008C12Y115/01001C12Y304/21022C12Y401/01028
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Abstract
The disclosure in some aspects, relates to nucleic acids, compositions and kits useful for gene therapy with reduced immune response to transgene products.
Claims (12)
1 . A method of delivering a transgene to a subject, the method comprising administering to the subject a recombinant Adeno-Associated Virus (rAAV) comprising the transgene, wherein the transgene encodes an RNA transcript that comprises two different immune-associated miRNA binding sites, wherein the two different immune-associated miRNA binding sites bind a miRNA pair selected from: (i) miR-142-3p and miR-155, (ii) miR-181a and miR-21, (iii) miR-16-1 and miR-150, (iv) miR-146 and miR-181la, (v) miR-31 and miR-181a, (vi) miR-146a and miR-16-1, (vii) miR-150 and miR-18 1a, (viii) miR-16-1 and miR-181a, and (ix) miR-142-3p and miR-223.
2 . The method of claim 1 , wherein the RNA transcript encodes a protein comprising a plurality of Glycine-Alanine repeats.
3 . The method of claim 1 , wherein the RNA transcript comprises at least one additional immune-associated miRNA binding sites.
4 . The method of claim 3 , wherein the RNA transcript comprises one to eight additional immune-associated miRNA binding sites.
5 . The method of claim 1 , wherein the RNA transcript is a messenger RNA comprising a 3′ UTR and at least one of the miRNA binding sites is present in the 3′-UTR of the messenger RNA.
6 . The method of claim 1 , wherein the RNA transcript is a messenger RNA comprising a 3′ UTR and each of the miRNA binding sites is present in the 3′-UTR of the messenger RNA.
7 . The method of claim 1 , wherein the RNA transcript encodes a therapeutic protein.
8 . The method of claim 7 , wherein the therapeutic protein is selected from the group consisting of: aromatic L-amino acid decarboxylase (AADC), frataxin, superoxide Dismutase 1 (SOD1), insulin, Human Factor IX, a tumour necrosis factor (TNF)-specific antibody, a human epidermal growth factor receptor 2 (HER2)-specific antibody, a vascular endothelial growth factor A (VEGFA)-specific antibody, a CD20-specific antibody, a TNF-a-specific antibody, a HER 1-specific antibody, a CTLA-4-specific antibody, a BAFF-specific antibody, an HIV-specific antibody, a CD1la-specific antibody, a CD25-specific antibody, a CD30-specific antibody, a CD33-specific antibody, and a CD52-specific antibody.
9 . The method of claim 7 , wherein the therapeutic protein comprises an antigen-binding protein, an antigen-binding protein fragment, an immunoglobulin heavy chain, or a light chain.
10 . The method of claim 1 , wherein the RNA transcript encodes a protein comprising between 2 and 20 Glycine-Alanine repeats.
11 . The method of claim 1 , wherein the rAAV comprises an AAV1 capsid protein, an AAV2 capsid protein, an AAV3 capsid protein, an AAV4 capsid protein, an AAV5 capsid protein, an AAV6 capsid protein, an AAV7 capsid protein, an AAV8 capsid protein, an AAV9 capsid protein, an AAV10 capsid protein, an AAV11 capsid protein, or an AAV12 capsid protein.
12 . The method of claim 1 , wherein the transgene is flanked by inverted terminal repeat (ITR) sequences.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 3, 2021
From: ZAMORE, PHILLIP D.
To: HOWARD HUGHES MEDICAL INSTITUTE
Reel/Frame 056424/0847 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 3, 2021
From: GAO, GUANGPING; ZAMORE, PHILLIP D.; LI, SHAOYONG; HOWARD HUGHES MEDICAL INSTITUTE
To: UNIVERSITY OF MASSACHUSETTS
Reel/Frame 056424/0918 →
Continuity (4)
Continuation
15306543
Provisional Application
62001280
· May 21, 2014
Provisional Application
61984460
· Apr 25, 2014
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