Granted Patent
B2
US 12,467,064 · App. 17/283,232 · Granted Nov 11, 2025
Artificial expression constructs for selectively modulating gene expression in interneurons
Inventors:
Jonathan Ting (Lake Forest Park, WA); Boaz P. Levi (Seattle, WA); John K. Mich (Seattle, WA); Edward Sebastian Lein (Mercer Island, WA); Franck Kalume (Bothell, WA)
C12N15/86A01K67/0278A61K35/30C12N5/0619A01K2217/052A01K2227/105A01K2227/106C12N2510/00C12N2750/14043
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Abstract
Artificial expression constructs for selectively modulating gene expression in selected central nervous system cell types are described. The artificial expression constructs can be used to selectively express synthetic genes or modify gene expression in GABAergic interneurons.
Claims (18)
1 . An artificial expression construct comprising (i) a concatemer comprising 2, 3, 4, 5, 6, 7, 8, 9, or 10 copies of a sequence consisting of SEQ ID NO: 2 or SEQ ID NO: 6; (ii) a promoter; and (iii) a coding sequence.
2 . The artificial expression construct of claim 1 , wherein the coding sequence encodes a fluorescent protein or an ion transporter selected from a potassium channel, or a calcium channel.
3 . The artificial expression construct of claim 1 , within a vector for delivery into a cell.
4 . The artificial expression construct of claim 3 , wherein the vector is a viral vector.
5 . The artificial expression construct of claim 4 , wherein the viral vector is a recombinant adeno-associated viral (AAV) vector.
6 . The artificial expression construct of claim 1 , wherein the concatemer comprises 2, 3, 4, 5, or 6 copies of the sequence consisting of SEQ ID NO: 2 or 2, 3, 4, 5, or 6 copies of the sequence consisting of SEQ ID NO: 6.
7 . The artificial expression construct of claim 1 , wherein the concatemer has 3 copies of the sequence consisting of SEQ ID NO: 2 or 3 copies of the sequence consisting of SEQ ID NO: 6.
8 . The artificial expression construct of claim 1 , wherein the concatemer consists of the sequence of SEQ ID NO: 3 or SEQ ID NO: 7.
9 . The artificial expression construct of claim 1 , wherein the artificial expression construct is associated with a capsid that crosses the blood brain barrier.
10 . The artificial expression construct of claim 9 , wherein the capsid is PHP.eB, AAV-BR1, AAV-PHP.S, AAV-PHP.B, or AAV-PPS.
11 . The artificial expression construct of claim 1 , wherein the artificial expression construct encodes a skipping element.
12 . The artificial expression construct of claim 11 , wherein the skipping element comprises a 2A peptide or an internal ribosome entry site (IRES).
13 . The artificial expression construct of claim 12 , wherein the 2A peptide is selected from T2A, P2A, E2A, or F2A.
14 . The artificial expression construct of claim 1 , wherein the artificial expression construct encodes a set of features selected from: 3Xhl56Core, minBglobin, minCMV, SYFP2, His, 3×HA, NavMs, NavBp, NavSheP-D60N, WPRE3, or BGHpA.
15 . The artificial expression construct of claim 1 , comprising a sequence having at least 95% sequence identity to the sequence of SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, or SEQ ID NO: 42.
16 . The artificial expression construct of claim 1 , having the sequence of SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, or SEQ ID NO: 42.
17 . The artificial expression construct of claim 5 , wherein the AAV vector is replication-competent.
18 . The artificial expression construct of claim 1 , wherein the coding sequence encodes an ion transporter, an enzyme, a transcription factor, a receptor, a membrane protein, a cellular trafficking protein, a signaling molecule, a neurotransmitter, a calcium reporter, a channel rhodopsin, a CRISPR/CAS molecule, an editase, a guide RNA molecule, a homologous recombination donor cassette, or a designer receptor exclusively activated by designer drug (DREADD).
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 9, 2025
From: TING, JONATHAN; LEVI, BOAZ P.; MICH, JOHN K.; LEIN, EDWARD SEBASTIAN
To: ALLEN INSTITUTE
Reel/Frame 071078/0571 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 9, 2025
From: KALUME, FRANCK
To: SEATTLE CHILDREN'S HOSPITAL (D/B/A SEATTLE CHILDREN'S RESEARCH INSTITUTE)
Reel/Frame 071078/0664 →
CONFIRMATORY LICENSE
Recorded Jan 30, 2024
From: ALLEN INSTITUTE
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066378/0836 →
Continuity (4)
Provisional Application
62810281
· Feb 25, 2019
Provisional Application
62749012
· Oct 22, 2018
Provisional Application
62742835
· Oct 8, 2018
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