IP Library › Granted Patent US 12674181
Granted Patent B2
US 12674181 · App. 18/252,498 · Granted Jul 7, 2026

Artificial expression constructs for modulating gene expression in chandelier cells

Inventors: Tanya Daigle (Seattle, WA); Lucas T. Graybuck (Seattle, WA); Brian Edward Kalmbach (Poulsbo, WA); Edward Sebastian Lein (Seattle, WA); John K. Mich (Seattle, WA); Boaz P. Levi (Seattle, WA); Adriana Estela Sedeño Cortés (Seattle, WA); Bosiljka Tasic (Seattle, WA); Jonathan Ting (Seattle, WA); Hongkui Zeng (Seattle, WA)
Assignee: Allen Institute
C12N15/86C12N2750/14143C12N2750/14171C12N2830/008
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12674181
App. No.
18/252,498
Granted
Jul 7, 2026
Kind
B2
Abstract

Artificial expression constructs for modulating gene expression in targeted central nervous system cell types are described. The artificial expression constructs can be used to express synthetic genes or modify gene expression in chandelier cells. Chandelier cells are a subtype of GABAergic interneurons that that have been implicated in disorders such as epilepsy and schizophrenia.

Claims (13)

1 . A concatemer having 2, 3, 4, 5, 6, 7, 8, 9, or 10 copies of a sequence as set forth in SEQ ID NO: 8.

2 . The concatemer of claim 1 , wherein the concatemer has a sequence as set forth in SEQ ID NO: 9 or a sequence having at least 98% sequence identity to the sequence as set forth in SEQ ID NO: 9.

3 . An artificial expression construct comprising:

(i) the concatemer of claim 1 ; (ii) a promoter; and (iii) a heterologous encoding sequence.

4 . The artificial expression construct of claim 3 , wherein the heterologous encoding sequence encodes a fluorescent protein.

5 . The artificial expression construct of claim 3 , wherein the heterologous encoding sequence encodes a neurotransmitter.

6 . The artificial expression construct of claim 3 , wherein the artificial expression construct is associated with a capsid that crosses the blood brain barrier.

7 . The artificial expression construct of claim 6 , wherein the capsid comprises PHP.eB, AAV-BR1, AAV-PHP.S, AAV-PHP.B, AAV9, AAVrh.10, or AAV-PPS.

8 . The artificial expression construct of claim 3 , wherein the artificial expression construct comprises or encodes a skipping element.

9 . The artificial expression construct of claim 8 , wherein the skipping element comprises a T2A, P2A, E2A, or F2A peptide and/or an internal ribosome entry site (IRES).

10 . The artificial expression construct of claim 3 , wherein the artificial expression construct encodes a Gly-Ser linker.

11 . The artificial expression construct of claim 3 , wherein the artificial expression construct encodes a nuclear localization protein comprising Histone H1, Histone H2A, Histone H2B, Histone H3, Histone H4, and/or histone-like protein HPhA.

12 . The artificial expression construct of claim 3 , wherein the artificial expression construct is within a viral vector.