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Title:
METHODS AND COMPOSITIONS FOR MODULATING GOBLET CELLS AND FOR MUCO-OBSTRUCTIVE DISEASES
Document Type and Number:
WIPO Patent Application WO/2023/039164
Kind Code:
A3
Abstract:
The present disclosure relates, inter alia, to perturbagens and methods for directing a change in the cell state of an intestinal stem cell and/or a basal cell. It also relates to methods for increasing a quantity of goblet progenitors, goblet cells, Paneth cells, and/or enteroendocrine cells or immediate progenitors thereof and/or the ratios thereof, and methods for decreasing the function and quantity of goblet cells or immediate progenitors thereof. Further, the present disclosure relates to methods for treating diseases or disorders characterized by, at least, abnormal function, abnormal ratios and/or abnormal numbers of goblet progenitors, goblet cells, Paneth cells, and/or enteroendocrine cells, or immediate progenitors thereof.

Inventors:
STEWART MORAG (US)
CHALKIADAKI ANGELIKI (US)
JI YUGE (US)
WOLF FABIAN (US)
PLUGIS NICHOLAS (US)
HOSSEINI POORYA (US)
LIPCHINA INNA (US)
TRITSCHLER SOPHIE (US)
Application Number:
PCT/US2022/043059
Publication Date:
April 20, 2023
Filing Date:
September 09, 2022
Export Citation:
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Assignee:
FLAGSHIP PIONEERING INNOVATIONS VI LLC (US)
International Classes:
C12N5/071; C12Q1/6809
Domestic Patent References:
WO2021146432A12021-07-22
Foreign References:
US20210040442A12021-02-11
US20190263912A12019-08-29
US20200020419A12020-01-16
US20150190432A12015-07-09
Other References:
XIAOLEI YIN ET AL: "Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny", NATURE METHODS, vol. 11, no. 1, 1 December 2013 (2013-12-01), New York, pages 106 - 112, XP055292181, ISSN: 1548-7091, DOI: 10.1038/nmeth.2737
BASAK ONUR ET AL: "Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells", CELL STEM CELL, ELSEVIER, CELL PRESS, AMSTERDAM, NL, vol. 20, no. 2, 8 December 2016 (2016-12-08), pages 177, XP029906326, ISSN: 1934-5909, DOI: 10.1016/J.STEM.2016.11.001
LIU YUAN ET AL: "Monolayer culture of intestinal epithelium sustains Lgr5+ intestinal stem cells", CELL DISCOVERY, vol. 4, no. 1, 12 June 2018 (2018-06-12), XP093013338, Retrieved from the Internet DOI: 10.1038/s41421-018-0036-z
ZHAO ANDONG ET AL: "Chemical conversion of human epidermal stem cells into intestinal goblet cells for modeling mucus-microbe interaction and therapy", SCI. ADV, vol. 7, 14 April 2021 (2021-04-14), pages 1 - 17, XP093013341
VIEIRA BRAGA FELIPE A ET AL: "A cellular census of human lungs identifies novel cell states in health and in asthma", NATURE MEDICINE, NATURE PUBLISHING GROUP US, NEW YORK, vol. 25, no. 7, 17 June 2019 (2019-06-17), pages 1153 - 1163, XP036829223, ISSN: 1078-8956, [retrieved on 20190617], DOI: 10.1038/S41591-019-0468-5
ADAM L. HABER ET AL: "A single-cell survey of the small intestinal epithelium", NATURE, vol. 551, no. 7680, 8 November 2017 (2017-11-08), London, pages 333 - 339, XP055543522, ISSN: 0028-0836, DOI: 10.1038/nature24489
TREVEIL A. ET AL: "Regulatory network analysis of Paneth cell and goblet cell enriched gut organoids using transcriptomics approaches", MOLECULAR OMICS, vol. 16, no. 1, 1 January 2020 (2020-01-01), pages 39 - 58, XP093013336, DOI: 10.1039/C9MO00130A
Attorney, Agent or Firm:
ALTIERI, Stephen, L. et al. (US)
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