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Artificial expression constructs for selectively modulating gene expression in interneurons
US12467064B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-12467064-B2 |
| Application number | US-201917283232-A |
| Country | US |
| Kind code | B2 |
| Filing date | Oct 3, 2019 |
| Priority date | Oct 8, 2018 |
| Publication date | Nov 11, 2025 |
| Grant date | Nov 11, 2025 |
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- Title
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Abstract
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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.
First claim
Opening claim text (preview).
What is claimed is: 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).
Assignees
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Classifications
viral genome or elements thereof as genetic vector · CPC title
Genetically modified cells · CPC title
Neurons · CPC title
Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue · CPC title
Primate · CPC title
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Frequently asked questions
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- What does patent US12467064B2 cover?
- 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.
- Who is the assignee on this patent?
- Allen Inst, Seattle Childrens Hospital
- What technology area does this patent fall under?
- Primary CPC classification C12N15/86. Mapped technology areas include Chemistry & Metallurgy.
- When was this patent published?
- Publication date Tue Nov 11 2025 00:00:00 GMT+0000 (Coordinated Universal Time) (B2). Legal status and post-grant events are not shown on this page.
- What related patents are in patentsdb?
- We list 4 related publications on this page (citations in our corpus or others sharing the same primary CPC).