Title:
DIRECT TRANSDIFFERENTIATION FOR TREATMENT OF NEUROLOGICAL DISEASE
Document Type and Number:
WIPO Patent Application WO/2023/051802
Kind Code:
A1
Abstract:
Provided are an RE1/NRSE element as a target for transdifferentiation of non-neuronal cells into neuronal cells, and the use of an RE1/NRSE blocker in the prevention and/or treatment of diseases associated with loss of function or death of neurons. Also provided is a method for blocking an RE1/NRSE element so as to regulate the expression of a neuron-associated gene in non-neuronal cells. The method comprises reducing binding of REST to an RE1/NRSE element or reducing the amount or activity of REST. Also provided is an RE1/NRSE element blocker, particularly a binding structural domain of an endogenous RE1/NRSE binding protein and a variant thereof, which can be used for the prevention and/or treatment of diseases associated with loss of function or death of neurons.
Inventors:
ZHOU HAIBO (CN)
HU XINDE (CN)
SU JINLIN (CN)
HU XINDE (CN)
SU JINLIN (CN)
Application Number:
PCT/CN2022/123409
Publication Date:
April 06, 2023
Filing Date:
September 30, 2022
Export Citation:
Assignee:
CENTER FOR EXCELLENCE IN BRAIN SCIENCE AND INTELLIGENCE TECH CHINESE ACADEMY OF SCIENCES (CN)
International Classes:
A61K31/713; A61K31/551; A61P25/00; C07K14/47; C12N15/113
Domestic Patent References:
| WO2021102345A1 | 2021-05-27 |
Foreign References:
| US20150299698A1 | 2015-10-22 | |||
| CN112566640A | 2021-03-26 | |||
| US20160031958A1 | 2016-02-04 |
Other References:
HWANG JEE-YEON, ZUKIN R SUZANNE: "REST, a master transcriptional regulator in neurodegenerative disease", CURRENT OPINION IN NEUROBIOLOGY, vol. 48, 1 February 2018 (2018-02-01), GB , pages 193 - 200, XP093052784, ISSN: 0959-4388, DOI: 10.1016/j.conb.2017.12.008
SHIMOJO MASAHITO, LEE JEONG-HEON, HERSH LOUIS B.: "Role of Zinc Finger Domains of the Transcription Factor Neuron-restrictive Silencer Factor/Repressor Element-1 Silencing Transcription Factor in DNA Binding and Nuclear Localization", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 276, no. 16, 1 April 2001 (2001-04-01), US , pages 13121 - 13126, XP093052785, ISSN: 0021-9258, DOI: 10.1074/jbc.M011193200
KONG QING-RAN, XIE BING-TENG, ZHANG HENG, LI JING-YU, HUANG TIAN-QING, WEI REN-YUE, LIU ZHONG-HUA: "RE1-silencing Transcription Factor (REST) Is Required for Nuclear Reprogramming by Inhibiting Transforming Growth Factor β Signaling Pathway", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 291, no. 53, 1 December 2016 (2016-12-01), US , pages 27334 - 27342, XP093052786, ISSN: 0021-9258, DOI: 10.1074/jbc.M116.743849
ALTSCHUL S.F ET AL., J. MOLECULAR BIOLOGY, vol. 215, 1990, pages 403 - 410
STEPHEN F. ET AL., NUCLEIC ACIDS RES., vol. 25, 1997, pages 3389 - 3402
HIGGINS D.G. ET AL., METHODS IN ENZYMOLOGY, vol. 266, 1996, pages 383 - 402
LARKIN M.A ET AL., BIOINFORMATICS (OXFORD, ENGLAND, vol. 23, no. 21, 2007, pages 2947 - 8
SHIMOJO MASAHITO, LEE JEONG-HEON, HERSH LOUIS B.: "Role of Zinc Finger Domains of the Transcription Factor Neuron-restrictive Silencer Factor/Repressor Element-1 Silencing Transcription Factor in DNA Binding and Nuclear Localization", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 276, no. 16, 1 April 2001 (2001-04-01), US , pages 13121 - 13126, XP093052785, ISSN: 0021-9258, DOI: 10.1074/jbc.M011193200
KONG QING-RAN, XIE BING-TENG, ZHANG HENG, LI JING-YU, HUANG TIAN-QING, WEI REN-YUE, LIU ZHONG-HUA: "RE1-silencing Transcription Factor (REST) Is Required for Nuclear Reprogramming by Inhibiting Transforming Growth Factor β Signaling Pathway", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 291, no. 53, 1 December 2016 (2016-12-01), US , pages 27334 - 27342, XP093052786, ISSN: 0021-9258, DOI: 10.1074/jbc.M116.743849
ALTSCHUL S.F ET AL., J. MOLECULAR BIOLOGY, vol. 215, 1990, pages 403 - 410
STEPHEN F. ET AL., NUCLEIC ACIDS RES., vol. 25, 1997, pages 3389 - 3402
HIGGINS D.G. ET AL., METHODS IN ENZYMOLOGY, vol. 266, 1996, pages 383 - 402
LARKIN M.A ET AL., BIOINFORMATICS (OXFORD, ENGLAND, vol. 23, no. 21, 2007, pages 2947 - 8
Attorney, Agent or Firm:
SHANGHAI PATENT & TRADEMARK LAW OFFICE, LLC (CN)
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