IP Library › Granted Patent US 12,285,496
Granted Patent B2
US 12,285,496 · App. 17/963,901 · Granted Apr 29, 2025

Gene therapy for haploinsufficiency

Inventors: Nadav Ahituv (San Francisco, CA); Navneet Matharu (San Francisco, CA)
Assignee: The Regents of the University of California
A61K48/0066A01K67/0276A61K48/0016A61P3/04C12N9/22C12N15/102C12N15/113C12N15/86A01K2217/077A01K2227/105A01K2267/0362C12N2310/20
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Quick Facts
Patent No.
US 12,285,496
App. No.
17/963,901
Granted
Apr 29, 2025
Kind
B2
Abstract

Methods and compositions are provided for activating transcription in a mammalian cell.

Claims (8)

1. A composition comprising an adeno-associated viral vector comprising a nucleic acid encoding a guide RNA, wherein the guide RNA comprises:

a) a targeting region that, under conditions present in a nucleus of a cell, specifically hybridizes to a promoter region or an enhancer region operably linked to a wild-type copy of a haploinsufficient gene; and

b) a binding region that specifically binds a catalytically inactive CRISPR nuclease under conditions present in the nucleus of the cell, wherein the haploinsufficient gene is SCN2A, SIM1, or MC4R.

2. The composition of claim 1 , wherein the catalytically inactive CRISPR nuclease comprises (i) a nuclease domain that has been modified to eliminate nuclease and nicking activity and (ii) a transcriptional activation domain, and/or a D10A, H840A S. pyogenes dCas9.

3. The composition of claim 1 , wherein the catalytically inactive CRISPR nuclease is a catalytically inactive CRISPR nuclease-VP64 fusion polypeptide.

4. The composition of claim 1 , wherein the cell is a non-dividing cell, a neuron, or a hypothalamus cell.

5. The composition of claim 1 , further comprising one or more plasmids encoding AAV rep and cap genes.

6. The composition of claim 1 , further comprising one or more plasmids encoding adenovirus helper factors E1A, E1B, E2A, E4ORF6, and/or VA.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 7, 2025
From: AHITUV, NADAV; MATHARU, NAVNEET
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 069767/0440 →
Continuity (3)
Division 16479177
Provisional Application 62455988 · Feb 7, 2017
Related Publication 20230293729A1 · Sep 21, 2023
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