WO2020076614A1 - Artificial expression constructs for selectively modulating gene expression in interneurons - Google Patents

Artificial expression constructs for selectively modulating gene expression in interneurons Download PDF

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Publication number
WO2020076614A1
WO2020076614A1 PCT/US2019/054539 US2019054539W WO2020076614A1 WO 2020076614 A1 WO2020076614 A1 WO 2020076614A1 US 2019054539 W US2019054539 W US 2019054539W WO 2020076614 A1 WO2020076614 A1 WO 2020076614A1
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seq
protein
molecule
expression construct
vector
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English (en)
French (fr)
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Jonathan Ting
Boaz P. LEVI
John K. Mich
Edward Sebastian LEIN
Franck KALUME
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Seattle Children's Hospital
Allen Institute
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Seattle Children's Hospital
Allen Institute
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Priority to AU2019358806A priority Critical patent/AU2019358806B2/en
Priority to US17/283,232 priority patent/US12467064B2/en
Priority to EP19870829.9A priority patent/EP3864150A4/en
Priority to CA3115652A priority patent/CA3115652A1/en
Priority to JP2021543981A priority patent/JP7695192B2/ja
Application filed by Seattle Children's Hospital, Allen Institute filed Critical Seattle Children's Hospital
Publication of WO2020076614A1 publication Critical patent/WO2020076614A1/en
Anticipated expiration legal-status Critical
Priority to JP2024187194A priority patent/JP7829658B2/ja
Priority to US19/007,152 priority patent/US20250223612A1/en
Priority to AU2025208516A priority patent/AU2025208516A1/en
Priority to JP2026032511A priority patent/JP2026094314A/ja
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Definitions

  • the product of the coding sequence may be expressed at low levels in non-selected cell types, for example at less than 1 % or 1 %, 2%, 3%, 5%, 10%, 15% or 20% of the levels at which the product is expressed in selected neural cells.
  • the targeted central nervous system cell type is the only cell type that expresses the right combination of transcription factors that bind an enhancer disclosed herein to drive gene expression. Thus, in particular embodiments, expression occurs exclusively within the targeted cell type.
  • Serpinfl Found in many cortical layers, and have molecular overlaps with Sncg and Vip cells, but inconsistent expression of Sncg or Vip, with more consistent expression of Serpinfl
  • L2/3 IT Primarily reside in Layer 2/3 and have mainly intratelencephalic (cortico-cortical) projections.
  • GCaMPs yield distinct fluorescence emission spectra (Zhao et al..Science, 201 1 , 333(6051): 1888-1891).
  • Exemplary GECIs with green fluorescence include GCaMP3, GCaMP5G, GCaMP6s, GCaMP6m, GCaMP6f, jGCaMP7s, jGCaMP7c, jGCaMP7b, andjGCaMP7f.
  • GECIs with red fluorescence include jRGECOIa and jRGECOI b.
  • AAV products containing GECIs are commercially available. For example, Vigene Biosciences provides AAV products including AAV8-CAG-GCaMP3 (Cat.
  • Additional effector elements include Cre, iCre, dgCre, FlpO, and tTA2.
  • iCre refers to a codon-improved Cre.
  • dgCre refers to an enhanced GFP/Cre recombinase fusion gene with an N terminal fusion of the first 159 amino acids of the Escherichia coli K-12 strain chromosomal dihydrofolate reductase gene (DHFR or folA) harboring a G67S mutation and modified to also include the R12Y/Y100I destabilizing domain mutation.
  • FlpO refers to a codon-optimized form of FLPe that greatly increases protein expression and FRT recombination efficiency in mouse cells. Like the Cre/LoxP system, the FLP/FRT system has been widely used for gene expression (and generating conditional knockout mice, mediated by the FLP/FRT system).
  • tTA2 refers to tetracycline transactivator.
  • Adeno-Associated Virus is a parvovirus, discovered as a contamination of adenoviral stocks. It is a ubiquitous virus (antibodies are present in 85% of the US human population) that has not been linked to any disease. It is also classified as a dependovirus, because its replication is dependent on the presence of a helper virus, such as adenovirus. Various serotypes have been isolated, of which AAV-2 is the best characterized. AAV has a single-stranded linear DNA that is encapsidated into capsid proteins VP1 , VP2 and VP3 to form an icosahedral virion of 20 to 24 nm in diameter.
  • Polyadenylation sequences can promote mRNA stability by addition of a poly(A) tail to the 3' end of the coding sequence and thus, contribute to increased translational efficiency.
  • Particular embodiments may utilize BGHpA or SV40pA.
  • a preferred embodiment of an expression construct includes a terminator element. These elements can serve to enhance transcript levels and to minimize read through from the construct into other plasmid sequences.
  • Pharmaceutically-acceptable salts include the acid addition salts (formed with the free amino groups of the protein) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, histidine, procaine and the like.
  • inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like.
  • Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethyl
  • (iii) Cell Lines Including Artificial Expression Constructs The present disclosure includes cells including an artificial expression construct described herein.
  • a cell that has been transformed with an artificial expression construct can be used for many purposes, including in neuroanatomical studies, assessments of functioning and/or non-functioning proteins, and drug screens that assess the regulatory properties of enhancers.
  • the cell is a mammalian neural cell.
  • the enhancer sequence of the artificial expression construct is SEQ ID NO: 3 and/or 7 and/or a CN1390, CN1244, CN1389, CN1203, CN1367, CN1498, CN1499, CN1500, CN1838 or a combination of components depicted in FIG. 16, and the cell line is a human, primate, or murine neural cell.
  • Cell lines which can be utilized for transgenesis in the present disclosure also include primary cell lines derived from living tissue such as rat or mouse brains and organotypic cell cultures, including brain slices from animals such as rats or mice.
  • the PC12 cell line (available from the American Type Culture Collection, ATCC, Manassas, VA) has been shown to express a number of neuronal marker proteins in response to Neuronal Growth Factor (NGF).
  • NGF Neuronal Growth Factor
  • the PC12 cell line is considered to be a neuronal cell line and is applicable for use with this disclosure.
  • JAR cells (available from ATCC) are a platelet derived cell-line that express some neuronal genes, such as the serotonin transporter gene, and may be used with embodiments described herein.
  • Dravet syndrome is a drug-resistant and life-threatening form of epilepsy. It typically begins in the first year of life, with fever- or temperature- induced seizures that evolve into generalized clonic, tonic-clonic, and unilateral seizures. These seizures are often resistant to current anti-epileptic drugs, the first-line therapies for this syndrome; complete seizure control is typically not achieved. As the disease progresses, most affected children also suffer from comorbid conditions including developmental delays, intellectual disabilities, impaired motor control and coordination, autistic behaviors, sleep disturbances, and many die prematurely.

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PCT/US2019/054539 2018-10-08 2019-10-03 Artificial expression constructs for selectively modulating gene expression in interneurons Ceased WO2020076614A1 (en)

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Application Number Priority Date Filing Date Title
AU2019358806A AU2019358806B2 (en) 2018-10-08 2019-10-03 Artificial expression constructs for selectively modulating gene expression in interneurons
US17/283,232 US12467064B2 (en) 2018-10-08 2019-10-03 Artificial expression constructs for selectively modulating gene expression in interneurons
EP19870829.9A EP3864150A4 (en) 2018-10-08 2019-10-03 ARTIFICIAL EXPRESSION CONSTRUCTS FOR SELECTIVE MODULATION OF GENE EXPRESSION IN INTERNEURONES
CA3115652A CA3115652A1 (en) 2018-10-08 2019-10-03 Artificial expression constructs for selectively modulating gene expression in interneurons
JP2021543981A JP7695192B2 (ja) 2018-10-08 2019-10-03 介在ニューロンにおける遺伝子発現を選択的に調節するための人工発現構築物
JP2024187194A JP7829658B2 (ja) 2018-10-08 2024-10-24 介在ニューロンにおける遺伝子発現を選択的に調節するための人工発現構築物
US19/007,152 US20250223612A1 (en) 2018-10-08 2024-12-31 Artificial expression constructs for selectively modulating gene expression in interneurons
AU2025208516A AU2025208516A1 (en) 2018-10-08 2025-07-25 Artificial Expression Constructs For Selectively Modulating Gene Expression In Interneurons
JP2026032511A JP2026094314A (ja) 2018-10-08 2026-03-02 介在ニューロンにおける遺伝子発現を選択的に調節するための人工発現構築物

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US201862742835P 2018-10-08 2018-10-08
US62/742,835 2018-10-08
US201862749012P 2018-10-22 2018-10-22
US62/749,012 2018-10-22
US201962810281P 2019-02-25 2019-02-25
US62/810,281 2019-02-25

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US19/007,152 Continuation US20250223612A1 (en) 2018-10-08 2024-12-31 Artificial expression constructs for selectively modulating gene expression in interneurons

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021248085A2 (en) 2020-06-04 2021-12-09 Allen Institute Artificial expression constructs for selectively modulating gene expression in inhibitory neocortical neurons
WO2021216778A3 (en) * 2020-04-21 2021-12-16 Allen Institute Artificial expression constructs for selectively modulating gene expression in neocortical layer 5 glutamatergic neurons
WO2022036255A1 (en) * 2020-08-14 2022-02-17 Allen Institute Artificial expression constructs for modulating gene expression in striatal neurons
WO2022049385A1 (en) 2020-09-04 2022-03-10 Asklepios Biopharmaceutical, Inc. Regulatory nucleic acid sequences
WO2023250362A1 (en) * 2022-06-21 2023-12-28 Regel Therapeutics, Inc. Genetic regulatory elements and uses thereof
JP2024505027A (ja) * 2021-02-02 2024-02-02 アレン インスティテュート Ｇａｂａ作動性ニューロン及び星状膠細胞における遺伝子発現の調節のための人工発現構築物
US12121563B2 (en) 2018-04-09 2024-10-22 Allen Institute Rescuing voltage-gated sodium channel function in inhibitory neurons
JP7908261B2 (ja) 2020-08-14 2026-08-19 アレン インスティテュート 線条体ニューロンにおける遺伝子発現の調節のための人工発現構築物

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12467064B2 (en) * 2018-10-08 2025-11-11 Allen Institute Artificial expression constructs for selectively modulating gene expression in interneurons
CN116286917A (zh) * 2021-12-14 2023-06-23 中国科学院深圳先进技术研究院 重组载体及其构建方法和应用
EP4536835A2 (en) * 2022-06-13 2025-04-16 Allen Institute Artificial expression constructs for modulating gene expression in non-neuronal central nervous system cells
CN119060958A (zh) * 2023-12-15 2024-12-03 中国科学院深圳先进技术研究院 一种携带钙离子报告基因的神经元及其制备方法和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040087028A1 (en) * 1999-11-05 2004-05-06 Avigen Inc. Ecdysone-inducible adeno-associated virus expression vectors
US20180078658A1 (en) * 2015-03-31 2018-03-22 New York University Compositions and method for reducing seizures

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2002A (en) 1841-03-12 Tor and planter for plowing
US4736866B1 (en) 1984-06-22 1988-04-12 Transgenic non-human mammals
US5252334A (en) 1989-09-08 1993-10-12 Cygnus Therapeutic Systems Solid matrix system for transdermal drug delivery
US5399363A (en) 1991-01-25 1995-03-21 Eastman Kodak Company Surface modified anticancer nanoparticles
US5851832A (en) 1991-07-08 1998-12-22 Neurospheres, Ltd. In vitro growth and proliferation of multipotent neural stem cells and their progeny
US5766948A (en) 1993-01-06 1998-06-16 The Regents Of The University Of California Method for production of neuroblasts
US5543158A (en) 1993-07-23 1996-08-06 Massachusetts Institute Of Technology Biodegradable injectable nanoparticles
US6001654A (en) 1994-01-28 1999-12-14 California Institute Of Technology Methods for differentiating neural stem cells to neurons or smooth muscle cells using TGT-β super family growth factors
US5697899A (en) 1995-02-07 1997-12-16 Gensia Feedback controlled drug delivery system
IE80468B1 (en) 1995-04-04 1998-07-29 Elan Corp Plc Controlled release biodegradable nanoparticles containing insulin
US6048964A (en) 1995-12-12 2000-04-11 Stryker Corporation Compositions and therapeutic methods using morphogenic proteins and stimulatory factors
US5656016A (en) 1996-03-18 1997-08-12 Abbott Laboratories Sonophoretic drug delivery system
US5753506A (en) 1996-05-23 1998-05-19 Cns Stem Cell Technology, Inc. Isolation propagation and directed differentiation of stem cells from embryonic and adult central nervous system of mammals
US5797898A (en) 1996-07-02 1998-08-25 Massachusetts Institute Of Technology Microchip drug delivery devices
US5783208A (en) 1996-07-19 1998-07-21 Theratech, Inc. Transdermal drug delivery matrix for coadministering estradiol and another steroid
US5779708A (en) 1996-08-15 1998-07-14 Cyberdent, Inc. Intraosseous drug delivery device and method
US5968829A (en) 1997-09-05 1999-10-19 Cytotherapeutics, Inc. Human CNS neural stem cells
US6395546B1 (en) 2000-02-01 2002-05-28 Neurogeneration, Inc. Generation of dopaminergic neurons from human nervous system stem cells
AU2002250064B2 (en) 2001-02-13 2008-01-17 University Of Florida Research Foundation, Inc. A bi-directional dual promoter complex with enhanced promoter activity for transgene expression in eukaryotes
EP1430114B1 (en) 2001-09-14 2012-01-18 Stem Cell Therapeutics Inc. Prolactin induced increase in neural stem cell numbers and therapeutical use thereof
AU2003219933A1 (en) 2002-02-25 2003-09-09 Vanderbilt University Expression system for human brain-specific voltage-gated sodium channel, type 1
CA2693712C (en) 2007-07-14 2018-05-29 The University Of Iowa Research Foundation Methods and compositions for treating brain diseases
US20120308530A1 (en) 2011-06-03 2012-12-06 Beijing Allgens Medical Science & Technology Co., Ltd. Materials Composition and Methods to Control Neural Progenitor and Stem Cell Attachment, Proliferation and Guide Cell Differentiation
US20150044667A1 (en) 2012-03-20 2015-02-12 The Trustees Of The University Of Pennsylvania Human papillomavirus 16 (hpv16) - related epilepsy
US9579399B2 (en) 2012-08-27 2017-02-28 Friedrich Miescher Institute For Biomedical Research Retinal OFF circuit-specific promoter
DE102014207498A1 (de) 2014-04-17 2015-10-22 Universitätsklinikum Hamburg-Eppendorf Viraler Vektor für den zielgerichteten Gentransfer in Gehirn und Rückenmark
HUE049036T2 (hu) 2015-04-17 2020-09-28 P&X Medical Nv Összetételek és szerszámok glaukóma kezelésére
PL3298134T3 (pl) 2015-05-16 2023-09-18 Genzyme Corporation Edycja genów mutacji głęboko intronowych
AU2016366549B2 (en) 2015-12-11 2022-11-10 California Institute Of Technology Targeting peptides for directing adeno-associated viruses (AAVs)
CN117821509A (zh) * 2017-04-03 2024-04-05 编码治疗公司 组织选择性转基因表达
US11980671B2 (en) 2017-07-26 2024-05-14 Duke University Use of bacterial voltage gated ion channels for human therapies
EP3781174A4 (en) 2018-04-09 2022-01-26 Allen Institute RESCUE OF VOLTAGE CONTROLLED SODIUM CHANNEL FUNCTION IN INHIBITORY NEURONS
US12467064B2 (en) * 2018-10-08 2025-11-11 Allen Institute Artificial expression constructs for selectively modulating gene expression in interneurons

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040087028A1 (en) * 1999-11-05 2004-05-06 Avigen Inc. Ecdysone-inducible adeno-associated virus expression vectors
US20180078658A1 (en) * 2015-03-31 2018-03-22 New York University Compositions and method for reducing seizures

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE ncRNA [online] 5 December 2016 (2016-12-05), "PREDICTED: Panthera pardus uncharacterized LOC109263725 (LOC109263725) , transcript variant X2", Database accession no. XR_002078354 *
See also references of EP3864150A1 *

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12121563B2 (en) 2018-04-09 2024-10-22 Allen Institute Rescuing voltage-gated sodium channel function in inhibitory neurons
WO2021216778A3 (en) * 2020-04-21 2021-12-16 Allen Institute Artificial expression constructs for selectively modulating gene expression in neocortical layer 5 glutamatergic neurons
EP4162041A4 (en) * 2020-06-04 2024-10-16 Allen Institute ARTIFICIAL EXPRESSION CONSTRUCTS TO SELECTIVELY MODULATE GENE EXPRESSION IN INHIBITORY NEOCORTICAL NEURONS
WO2021248085A3 (en) * 2020-06-04 2022-01-13 Allen Institute Artificial expression constructs for selectively modulating gene expression in inhibitory neocortical neurons
JP7767324B2 (ja) 2020-06-04 2025-11-11 アレン インスティテュート 抑制性新皮質ニューロンにおいて遺伝子発現を選択的に調節する人工発現構築物
WO2021248085A2 (en) 2020-06-04 2021-12-09 Allen Institute Artificial expression constructs for selectively modulating gene expression in inhibitory neocortical neurons
JP2023529833A (ja) * 2020-06-04 2023-07-12 アレン インスティテュート 抑制性新皮質ニューロンにおいて遺伝子発現を選択的に調節する人工発現構築物
JP2026021417A (ja) * 2020-06-04 2026-02-10 アレン インスティテュート 抑制性新皮質ニューロンにおいて遺伝子発現を選択的に調節する人工発現構築物
US12692515B2 (en) 2020-06-04 2026-07-28 Allen Institute Artificial expression constructs for selectively modulating gene expression in inhibitory neocortical neurons
WO2022036255A1 (en) * 2020-08-14 2022-02-17 Allen Institute Artificial expression constructs for modulating gene expression in striatal neurons
JP7908261B2 (ja) 2020-08-14 2026-08-19 アレン インスティテュート 線条体ニューロンにおける遺伝子発現の調節のための人工発現構築物
JP2023537603A (ja) * 2020-08-14 2023-09-04 アレン インスティテュート 線条体ニューロンにおける遺伝子発現の調節のための人工発現構築物
EP4196583A4 (en) * 2020-08-14 2025-07-09 Allen Inst ARTIFICIAL EXPRESSION CONSTRUCTS TO MODULATE GENE EXPRESSION IN STRIATUM NEURONS
WO2022049385A1 (en) 2020-09-04 2022-03-10 Asklepios Biopharmaceutical, Inc. Regulatory nucleic acid sequences
EP4288064A4 (en) * 2021-02-02 2025-01-15 Allen Institute ARTIFICIAL EXPRESSION CONSTRUCTS TO MODULATE GENE EXPRESSION IN GABAERGIC NEURONS AND ASTROCYTES
JP2024505027A (ja) * 2021-02-02 2024-02-02 アレン インスティテュート Ｇａｂａ作動性ニューロン及び星状膠細胞における遺伝子発現の調節のための人工発現構築物
WO2023250362A1 (en) * 2022-06-21 2023-12-28 Regel Therapeutics, Inc. Genetic regulatory elements and uses thereof

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