IP Library › Granted Patent US 12,296,026
Granted Patent B2
US 12,296,026 · App. 16/966,521 · Granted May 13, 2025

Transcription regulatory elements and uses thereof

Inventor: John T. Gray (San Francisco, CA)
Assignee: Astellas Gene Therapies, Inc.
A61K48/0058A61P3/00C12N7/00C12N15/86C12N2750/14143C12N2830/008
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Quick Facts
Patent No.
US 12,296,026
App. No.
16/966,521
Granted
May 13, 2025
Kind
B2
Abstract

The invention provides regulatory elements, as well as vectors containing the same that may be used to stimulate transcription of a gene of interest in certain tissue types. The transcription regulatory elements described herein may be operably linked to a transgene, such as acid alpha-glucosidase (GAA), so as to promote expression of the GAA transgene in a cell, such as a muscle cell, liver cell, or neuron. The transcription regulatory elements described herein may be operably linked to a therapeutic transgene and used for the treatment of various disorders, such as lysosomal storage diseases, and particularly Pompe disease.

Claims (22)

1. A nucleic acid regulatory element comprising:

(i) a first segment;

(ii) a second segment; and

(iii) a third segment;

wherein the components are operably linked to each other in a 5′-to-3′ direction as:

first segment-second segment-third segment;

and wherein:

the first segment comprises a synapsin promoter having the nucleic acid sequence of SEQ ID NO: 8,

the second segment comprises an apolipoprotein E hepatic control region (ApoE-HCR) having the nucleic acid sequence of SEQ ID NO: 1, and

the third segment comprises a desmin promoter having the nucleic acid sequence of SEQ ID NO: 7.

2. A vector comprising the nucleic acid regulatory element of claim 1 , wherein the nucleic acid regulatory element is operably linked to a transgene, and wherein the nucleic acid regulatory element induces expression of the transgene upon introduction of the vector into a cell.

3. The vector of claim 2 , wherein:

(i) the transgene is acid alpha-glucosidase (GAA); and/or

(ii) the cell is a muscle cell, a neuron, or a hepatocyte.

4. The vector of claim 2 , wherein the vector is a viral vector.

5. The vector of claim 4 , wherein the viral vector is an adeno-associated virus (AAV).

6. The vector of claim 5 , wherein the AAV is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAVrh74 serotype.

7. The vector of claim 4 , wherein the viral vector is a pseudotyped AAV.

8. The vector of claim 7 , wherein the pseudotyped AAV is rAAV2/8 or rAAV2/9.

9. A composition comprising a nucleic acid molecule comprising the nucleic acid regulatory element of claim 1 , wherein the composition is a liposome, vesicle, synthetic vesicle, exosome, synthetic exosome, dendrimer, or nanoparticle.

10. A method of expressing a transgene in a cell, the method comprising contacting the cell with the vector of claim 2 for a time sufficient to stimulate transcription of the transgene in the cell.

11. A kit comprising the vector of claim 2 , wherein the kit further comprises a package insert instructing a user of the kit to contact the vector or composition with a cell, thereby expressing a transgene operably linked to the regulatory control element.

Assignments (2)
CHANGE OF NAME Recorded Aug 17, 2023
From: AUDENTES THERAPEUTICS, INC.
To: ASTELLAS GENE THERAPIES, INC.
Reel/Frame 064620/0439 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 9, 2021
From: GRAY, JOHN T.
To: AUDENTES THERAPEUTICS, INC.
Reel/Frame 055202/0366 →
Continuity (2)
Provisional Application 62626561 · Feb 5, 2018
Related Publication 20210162073A1 · Jun 3, 2021
References Cited (20)
US 8030065B2 · Gray · 2011 [cited by applicant]
US 8168425B2 · Gray · 2012 [cited by applicant]
US 20070161031A1 · Trinklein et al. · 2007 [cited by applicant]
US 20100120152A1 · Wooddell et al. · 2010 [cited by applicant]
US 20170218395A1 · Byrne et al. · 2017 [cited by applicant]
US 20170275649A1 · Vandendriessche et al. · 2017 [cited by applicant]
EP 1804839A2 · 2007 [cited by applicant]
EP 2438931A1 · 2012 [cited by applicant]
WO WO02095006A2 · 2002 [cited by applicant]
WO WO2015110449A1 · 2015 [cited by applicant]
WO WO2015196179A1 · 2015 [cited by applicant]
Gehrke (2003, Gene, 322:137-143). [cited by examiner]
Doerfler et al., “Copackaged AAV9 Vectors Promote Simultaneous Immune Tolerance and Phenotypic Correction of Pompe Disease,” Hum Gene Ther. 27(1):43-59 (2016). [cited by applicant]
Chu et al., “Induction of Immune Tolerance to a Therapuetic Protein by Intrathymic Gene Delivery,” Mol. Ther. 18(12):2146-54 (2010). [cited by applicant]
Gao et al., “A Novel Site, Mt, in the Human Desmin Enhancer is Necessary for Maximal Expression in Skeletal Muscle,” J Biol Chem. 273(11):6402-09 (1998) (9 pages). [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/US2019/016692, mailed Jun. 18, 2019 (20 pages). [cited by applicant]
Kwissa et al., “Efficient vaccination by intradermal or intramuscular inoculation of plasmid DNA expressing hepatitis B surface antigen under desmin promoter/enhancer control,” Vaccine. 18(22):2337-44 (2000). [cited by applicant]
Li et al., “High Level Desmin Expression Depends on a Muscle-specific Enhancer,” J Biol Chem. 256(10):6562-70 (1991). [cited by applicant]
Pacak et al., “Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in meonatal mice,” Genet Vaccine Ther. 6(13):doi: 10.1186/1479-0556-6-13 (2008) (… [cited by applicant]
Pacak, Christina A., Thesis: “Gene Delivery Strategies for The Treatment of Cardiac and Skeletal Muscle in Murine Models of Muscular Dystrophy,” Doctor of Philosophy, University of Florida, 2006 (151 pages). [cited by applicant]