Granted Patent
B2
US 12,630,824 · App. 18/426,444 · Granted May 19, 2026
RAAV-based compositions and methods
Inventors:
Terence Flotte (Worcester, MA); Christian Mueller (Worcester, MA); Phillip D. Zamore (Worcester, MA)
Assignee:
University of Massachusetts
C12N15/113A61K31/713A61K35/12A61K38/57A61K48/005A61K48/0058C07K14/8125C12N7/00C12N15/67C12N15/86C12N15/111C12N2310/141C12N2310/3519C12N2320/31C12N2750/14121C12N2750/14132C12N2750/14143
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Abstract
The invention relates to isolated nucleic acids and rAAV-based compositions, methods and kits useful for treating genetic diseases (e.g., alpha-1 antitrypsin deficiency).
Claims (30)
1 . A recombinant Adeno-Associated Virus (AAV) comprising an isolated nucleic acid comprising:
(a) a first region that encodes one or more first miRNAs comprising a nucleic acid having sufficient sequence complementary with an endogenous mRNA of a subject to hybridize with and inhibit expression of the endogenous mRNA, wherein the endogenous mRNA encodes a first protein; and
(b) a second region encoding an exogenous mRNA that encodes a second protein, wherein the second protein has an amino acid sequence that is at least 85% identical to the first protein,
wherein the one or more first miRNAs do not comprise a nucleic acid having sufficient sequence complementary to hybridize with and inhibit expression of the exogenous mRNA, and wherein the first region is positioned within an untranslated portion of the second region.
2 . The recombinant AAV of claim 1 , further comprising one or more capsid proteins of one or more AAV serotypes selected from the group consisting of: AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11 and variants thereof.
3 . A composition comprising the recombinant AAV of claim 1 .
4 . The composition of claim 3 , further comprising a pharmaceutically acceptable carrier.
5 . A kit comprising a container housing the composition of claim 3 .
6 . The kit of claim 5 , further comprising written instructions for administering the recombinant AAV to a subject.
7 . A method of expressing Alpha 1-Antitrypsin (AAT) protein in a subject, the method comprising:
administering to a subject an effective amount of a recombinant Adeno-Associated Virus (rAAV) of claim 1 .
8 . The method of claim 7 , wherein the rAAV is administered with a pharmaceutically acceptable carrier.
9 . The method of claim 7 , wherein the subject has or suspected of having an Alpha 1-Antitrypsin deficiency.
10 . The method of claim 7 , wherein the subject has a mutation in an AAT gene.
11 . The method of claim 7 , wherein administering to a subject comprises:
isolating cells or tissue from a subject;
contacting the cells or tissue with an effective amount of the recombinant Adeno-Associated Virus (rAAV), thereby producing transfected cells or tissue; and
administering the transfected cells or tissue to the subject.
12 . The method of claim 11 , wherein the administering the transfected cells or tissue to the subject is performed intravascularly, intravenously, intrathecally, intraperitoneally, intramuscularly, subcutaneously, or intranasally.
13 . The method of claim 11 , wherein the administering the transfected cells or tissue to the subject is performed by transplantation into a target tissue.
14 . The method of claim 13 , wherein the target tissue is liver or lung.
15 . A method of expressing Alpha 1-Antitrypsin (AAT) protein in a subject, the method comprising:
isolating cells or tissue from a subject;
contacting the cells or tissue with an effective amount of a recombinant Adeno-Associated Virus (rAAV) of claim 1 , thereby producing transfected cells or tissue; and
administering the transfected cells or tissue to the subject.
16 . The method of claim 15 , wherein the tissue is adipose tissue.
17 . The method of claim 15 , wherein the cells are stem cells derived from adipose tissue.
18 . The method of claim 15 , wherein the administering is performed intravascularly, intravenously, intrathecally, intraperitoneally, intramuscularly, subcutaneously, or intranasally.
19 . The method of claim 15 , wherein the administering the transfected cells or tissue to the subject is performed by transplantation into a target tissue.
20 . The method of claim 19 , wherein the target tissue is liver or lung.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 30, 2024
From: ZAMORE, PHILLIP D.
To: HOWARD HUGHES MEDICAL INSTITUTE
Reel/Frame 067263/0215 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 30, 2024
From: FLOTTE, TERENCE; MUELLER, CHRISTIAN; ZAMORE, PHILLIP D.; HOWARD HUGHES MEDICAL INSTITUTE
To: UNIVERSITY OF MASSACHUSETTS
Reel/Frame 067263/0330 →
Continuity (8)
Continuation
14113118
Provisional Application
61477671
· Apr 21, 2011
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