Title:
METHOD FOR CONTROLLING PROTEIN FUNCTION
Document Type and Number:
WIPO Patent Application WO/2023/068327
Kind Code:
A1
Abstract:
The present invention addresses the problem of: providing a method for reliably chemogenetically controlling the activity of a protein, and providing a protein used in this method. Specifically, the present invention is a plurality of protein fragments, wherein when assembled this plurality of protein fragments recovers the activity of the protein and wherein a degradation domain (DD) sequence is fused to each protein fragment of the plurality. The present invention is also a method for regulating the activity of a protein within a cell, said method comprising: a step for introducing into a cell the fusion products of a DD sequence and each fragment of a protein that has been divided such that upon assembly the activity of the protein is recovered; and a step for introducing a DD sequence-specific stabilization factor into the cell.
Inventors:
SATO MORITOSHI (JP)
KAWANO FUUN (JP)
KAWANO FUUN (JP)
Application Number:
PCT/JP2022/039087
Publication Date:
April 27, 2023
Filing Date:
October 20, 2022
Export Citation:
Assignee:
UNIV TOKYO (JP)
International Classes:
C07K2/00; C07K19/00; C12N15/09
Foreign References:
| RU2418859C1 | 2011-05-20 |
Other References:
ROBIDA, A.M. ; KERPPOLA, T.K.: "Bimolecular Fluorescence Complementation Analysis of Inducible Protein Interactions: Effects of Factors Affecting Protein Folding on Fluorescent Protein Fragment Association", JOURNAL OF MOLECULAR BIOLOGY, ACADEMIC PRESS, UNITED KINGDOM, vol. 394, no. 3, 4 December 2009 (2009-12-04), United Kingdom , pages 391 - 409, XP026749015, ISSN: 0022-2836, DOI: 10.1016/j.jmb.2009.08.069
CAROLIN SCHMELAS; DIRK GRIMM: "Split Cas9, Not Hairs − Advancing the Therapeutic Index of CRISPR Technology", BIOTECHNOLOGY JOURNAL, WILEY-VCH VERLAG, WEINHEIM, DE, vol. 13, no. 9, 2 February 2018 (2018-02-02), DE , XP072422815, ISSN: 1860-6768, DOI: 10.1002/biot.201700432
KALYN A. BROWN, ZOU YAN, SHIRVANYANTS DAVID, ZHANG JIE, SAMANTA SUBHAS, MANTRAVADI PAVAN K., DOKHOLYAN NIKOLAY V., DEITERS ALEXAND: "Light-cleavable rapamycin dimer as an optical trigger for protein dimerization", CHEMICAL COMMUNICATIONS, ROYAL SOCIETY OF CHEMISTRY, UK, vol. 51, no. 26, 1 January 2015 (2015-01-01), UK , pages 5702 - 5705, XP055499439, ISSN: 1359-7345, DOI: 10.1039/C4CC09442E
CAMACHO-SOTO KARLA, CASTILLO-MONTOYA JAVIER, TYE BLAKE, GHOSH INDRANEEL: "Ligand-Gated Split-Kinases", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 136, no. 10, 17 February 2014 (2014-02-17), pages 3995 - 4002, XP055869006, ISSN: 0002-7863, DOI: 10.1021/ja4130803
S. R. EDWARDS, T. J. WANDLESS: "The Rapamycin-binding Domain of the Protein Kinase Mammalian Target of Rapamycin Is a Destabilizing Domain", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 282, no. 18, 1 January 2007 (2007-01-01), pages 13395 - 13401, XP055048190, ISSN: 00219258, DOI: 10.1074/jbc.M700498200
GRAY, Daniel C. et al. Activation of Specific Apoptotic Caspases with an Engineered Small-Molecule-Activated Protease. Cell. 2010, vol. 142, pp. 637-646
CALDWELL REESE M., BERMUDEZ JESSICA G., THAI DAVID, AONBANGKHEN CHANAT, SCHUSTER BENJAMIN S., COURTNEY TAYLOR, DEITERS ALEXANDER, : "Optochemical Control of Protein Localization and Activity within Cell-like Compartments", BIOCHEMISTRY, vol. 57, no. 18, 8 May 2018 (2018-05-08), pages 2590 - 2596, XP093058665, ISSN: 0006-2960, DOI: 10.1021/acs.biochem.8b00131
CAROLIN SCHMELAS; DIRK GRIMM: "Split Cas9, Not Hairs − Advancing the Therapeutic Index of CRISPR Technology", BIOTECHNOLOGY JOURNAL, WILEY-VCH VERLAG, WEINHEIM, DE, vol. 13, no. 9, 2 February 2018 (2018-02-02), DE , XP072422815, ISSN: 1860-6768, DOI: 10.1002/biot.201700432
KALYN A. BROWN, ZOU YAN, SHIRVANYANTS DAVID, ZHANG JIE, SAMANTA SUBHAS, MANTRAVADI PAVAN K., DOKHOLYAN NIKOLAY V., DEITERS ALEXAND: "Light-cleavable rapamycin dimer as an optical trigger for protein dimerization", CHEMICAL COMMUNICATIONS, ROYAL SOCIETY OF CHEMISTRY, UK, vol. 51, no. 26, 1 January 2015 (2015-01-01), UK , pages 5702 - 5705, XP055499439, ISSN: 1359-7345, DOI: 10.1039/C4CC09442E
CAMACHO-SOTO KARLA, CASTILLO-MONTOYA JAVIER, TYE BLAKE, GHOSH INDRANEEL: "Ligand-Gated Split-Kinases", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 136, no. 10, 17 February 2014 (2014-02-17), pages 3995 - 4002, XP055869006, ISSN: 0002-7863, DOI: 10.1021/ja4130803
S. R. EDWARDS, T. J. WANDLESS: "The Rapamycin-binding Domain of the Protein Kinase Mammalian Target of Rapamycin Is a Destabilizing Domain", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 282, no. 18, 1 January 2007 (2007-01-01), pages 13395 - 13401, XP055048190, ISSN: 00219258, DOI: 10.1074/jbc.M700498200
GRAY, Daniel C. et al. Activation of Specific Apoptotic Caspases with an Engineered Small-Molecule-Activated Protease. Cell. 2010, vol. 142, pp. 637-646
CALDWELL REESE M., BERMUDEZ JESSICA G., THAI DAVID, AONBANGKHEN CHANAT, SCHUSTER BENJAMIN S., COURTNEY TAYLOR, DEITERS ALEXANDER, : "Optochemical Control of Protein Localization and Activity within Cell-like Compartments", BIOCHEMISTRY, vol. 57, no. 18, 8 May 2018 (2018-05-08), pages 2590 - 2596, XP093058665, ISSN: 0006-2960, DOI: 10.1021/acs.biochem.8b00131
Attorney, Agent or Firm:
OKUHARA Koji (JP)
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