Title:
COMPOSITION FOR ENHANCING REPROGRAMMING EFFICIENCY FROM SOMATIC CELL TO INDUCED PLURIPOTENT STEM CELL, COMPRISING MTOR ACTIVATOR, AND METHOD FOR ENHANCING REPROGRAMMING EFFICIENCY BY USING SAME
Document Type and Number:
WIPO Patent Application WO/2021/107715
Kind Code:
A1
Abstract:
The present invention relates to a composition for enhancing reprogramming efficiency from somatic cells to induced pluripotent stem cells, comprising an mTOR activator, and a method for enhancing reprogramming efficiency by using same. In the method, reprogramming factors including OCT4, SOX2, c-Myc, and KLF4 are transduced into somatic cells, followed by treatment with an mTOR activator, thereby remarkably increasing reprogramming efficiency into induced pluripotent stem cells. Therefore, the composition and method can be used for effectively inducing the reprograming of somatic cells into induced pluripotent stem cells.
Inventors:
KIM BYUNG SOO (KR)
LEE SEUNG JIN (KR)
LEE SEUNG JIN (KR)
Application Number:
PCT/KR2020/017172
Publication Date:
June 03, 2021
Filing Date:
November 27, 2020
Export Citation:
Assignee:
UNIV KOREA RES & BUS FOUND (KR)
International Classes:
C12N5/074
Foreign References:
| KR20190115394A | 2019-10-11 | |||
| KR20190076692A | 2019-07-02 |
Other References:
DUAN QINGRUI, LI SIYI, WEN XINRUI, SUNNASSEE GAVIN, CHEN JIAN, TAN SHENG, GUO YANG: "Valproic Acid Enhances Reprogramming Efficiency and Neuronal Differentiation on Small Molecules Staged-Induction Neural Stem Cells: Suggested Role of mTOR Signaling", FRONTIERS IN NEUROSCIENCE, vol. 13, no. 867, 1 January 2019 (2019-01-01), pages 1 - 14, XP055816007, DOI: 10.3389/fnins.2019.00867
JI-HYE JUNG, KA-WON KANG, JIHEA KIM, SOON-CHUL HONG, YONG PARK, BYUNG SOO KIM: "CXCR2 Inhibition in Human Pluripotent Stem Cells Induces Predominant Differentiation to Mesoderm and Endoderm Through Repression of mTOR, β-Catenin, and hTERT Activities", STEM CELLS AND DEVELOPMENT, MARY ANN LIEBERT, INC. PUBLISHERS, US, vol. 25, no. 13, 1 July 2016 (2016-07-01), US, pages 1006 - 1019, XP055755853, ISSN: 1547-3287, DOI: 10.1089/scd.2015.0395
YEON JA CHOI, YUN JUNG PARK, JI YOUNG PARK, HYOUNG OH JEONG, DAE HYUN KIM, YOUNG MI HA, JI MIN KIM, YU MIN SONG, HYOUNG-SAM HEO, B: "Inhibitory Effect of mTOR Activator MHY1485 on Autophagy: Suppression of Lysosomal Fusion", PLOS ONE, vol. 7, no. 8, pages e43418, XP055298347, DOI: 10.1371/journal.pone.0043418
S. GAO, H. TANG, BH. ZHOU, KL. TANG: "mTOR REGULATES THE PROLIFERATION AND DIFFERENTIATION OF TENDON STEM CELLS: AN IN VITRO STUDY", JOURNAL OF AGING RESEARCH & LIFESTYLE, vol. 6, pages 168 - 175, XP055816010, DOI: 10.14283/jarcp.2017.22
WANG SHUO, XIA PENGYAN, YE BUQING, HUANG GUANLING, LIU JING, FAN ZUSEN: "Transient Activation of Autophagy via Sox2-Mediated Suppression of mTOR Is an Important Early Step in Reprogramming to Pluripotency", CELL STEM CELL, ELSEVIER, CELL PRESS, AMSTERDAM, NL, vol. 13, no. 5, 1 November 2013 (2013-11-01), AMSTERDAM, NL, pages 617 - 625, XP055816019, ISSN: 1934-5909, DOI: 10.1016/j.stem.2013.10.005
LEE SEUNG-JIN, KANG KA-WON, KIM JI-HEA, LEE BYUNG-HYUN, JUNG JI-HYE, PARK YONG, HONG SOON-CHEOL, KIM BYUNG-SOO: "CXCR2 Ligands and mTOR Activation Enhance Reprogramming of Human Somatic Cells to Pluripotent Stem Cells", STEM CELLS AND DEVELOPMENT, MARY ANN LIEBERT, INC. PUBLISHERS, US, vol. 29, no. 3, 1 February 2020 (2020-02-01), US, pages 119 - 132, XP055799879, ISSN: 1547-3287, DOI: 10.1089/scd.2019.0188
LEE, SEUNG-JIN: "CXCR2 activation promotes the production of induced Pluripotent Stem Cells", PH.D. THESIS, 1 February 2020 (2020-02-01), pages 1 - 57, XP009528373
JI-HYE JUNG, KA-WON KANG, JIHEA KIM, SOON-CHUL HONG, YONG PARK, BYUNG SOO KIM: "CXCR2 Inhibition in Human Pluripotent Stem Cells Induces Predominant Differentiation to Mesoderm and Endoderm Through Repression of mTOR, β-Catenin, and hTERT Activities", STEM CELLS AND DEVELOPMENT, MARY ANN LIEBERT, INC. PUBLISHERS, US, vol. 25, no. 13, 1 July 2016 (2016-07-01), US, pages 1006 - 1019, XP055755853, ISSN: 1547-3287, DOI: 10.1089/scd.2015.0395
YEON JA CHOI, YUN JUNG PARK, JI YOUNG PARK, HYOUNG OH JEONG, DAE HYUN KIM, YOUNG MI HA, JI MIN KIM, YU MIN SONG, HYOUNG-SAM HEO, B: "Inhibitory Effect of mTOR Activator MHY1485 on Autophagy: Suppression of Lysosomal Fusion", PLOS ONE, vol. 7, no. 8, pages e43418, XP055298347, DOI: 10.1371/journal.pone.0043418
S. GAO, H. TANG, BH. ZHOU, KL. TANG: "mTOR REGULATES THE PROLIFERATION AND DIFFERENTIATION OF TENDON STEM CELLS: AN IN VITRO STUDY", JOURNAL OF AGING RESEARCH & LIFESTYLE, vol. 6, pages 168 - 175, XP055816010, DOI: 10.14283/jarcp.2017.22
WANG SHUO, XIA PENGYAN, YE BUQING, HUANG GUANLING, LIU JING, FAN ZUSEN: "Transient Activation of Autophagy via Sox2-Mediated Suppression of mTOR Is an Important Early Step in Reprogramming to Pluripotency", CELL STEM CELL, ELSEVIER, CELL PRESS, AMSTERDAM, NL, vol. 13, no. 5, 1 November 2013 (2013-11-01), AMSTERDAM, NL, pages 617 - 625, XP055816019, ISSN: 1934-5909, DOI: 10.1016/j.stem.2013.10.005
LEE SEUNG-JIN, KANG KA-WON, KIM JI-HEA, LEE BYUNG-HYUN, JUNG JI-HYE, PARK YONG, HONG SOON-CHEOL, KIM BYUNG-SOO: "CXCR2 Ligands and mTOR Activation Enhance Reprogramming of Human Somatic Cells to Pluripotent Stem Cells", STEM CELLS AND DEVELOPMENT, MARY ANN LIEBERT, INC. PUBLISHERS, US, vol. 29, no. 3, 1 February 2020 (2020-02-01), US, pages 119 - 132, XP055799879, ISSN: 1547-3287, DOI: 10.1089/scd.2019.0188
LEE, SEUNG-JIN: "CXCR2 activation promotes the production of induced Pluripotent Stem Cells", PH.D. THESIS, 1 February 2020 (2020-02-01), pages 1 - 57, XP009528373
Attorney, Agent or Firm:
KONG, Byung Wook (KR)
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