Title:
LIVER FIBROSIS INDUCING VECTOR AND METHOD FOR ESTABLISHING ANIMAL MODEL, USING SAME
Document Type and Number:
WIPO Patent Application WO/2018/236079
Kind Code:
A1
Abstract:
The present invention relates to a liver fibrosis inducing vector and a method for establishing an animal model, using the same. According to the present invention, treatment with tamoxifen at a specific time point allows a Cas9-ERT2 protein complex to translocate from the cytosol into the nucleus. As such, the protein complex that has translocated into the nucleus can more elaborately modify a specific DNA in a desired part at a desired time point with the aid of guide RNA (gRNA). Particularly, application of tamoxifen to a Cas9-ERT2 complex in which a gRNA of the liver fibrosis regulator gene TIF1γ is fused to a hepatic stellate cell-specific promoter knocks out the TIF1γ gene to cause liver fibrosis. TIF1γ is a very important factor in the prevention and treatment of liver fibrosis or liver cirrhosis. Therefore, the present invention can be utilized for developing a technology for analysis of liver fibrosis disease and further is useful for clinical studies such as screening of candidate drugs for treatment of liver fibrosis, with the expectation of finding applications to identifying novel proteins that may be targets of new drug development.
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Inventors:
LEE EUN JU (KR)
KIM HYO-SOO (KR)
KIM HYO-SOO (KR)
Application Number:
PCT/KR2018/006451
Publication Date:
December 27, 2018
Filing Date:
June 07, 2018
Export Citation:
Assignee:
SEOUL NAT UNIV HOSPITAL (KR)
International Classes:
C12N15/85; A01K67/027; C07K14/72; C12N9/22; C12N15/10; C12N15/113
Domestic Patent References:
| WO2015100929A1 | 2015-07-09 |
Other References:
"Addgene: pPB- US -ECasE", ADDGENE, 7 December 2016 (2016-12-07), pages 1 - 4, Retrieved from the Internet
HERQUEL, B. ET AL.: "Transcription Cofactors TRIM24, TRIM28, and TRIM33 Associate to Form Regulatory Complexes that Suppress Murine Hepatocellular Carcinoma", PNAS, vol. 108, no. 20, 2011, pages 8212 - 8217, XP055566603
GREENHALGH, S. N. ET AL.: "Cre-tivity in the Liver: Transgenic Approaches to Targeting Hepatic Nonparenchymal Cells", HEPATOLOG Y, vol. 61, no. 6, 2015, pages 2091 - 2099, XP055566613
DATABASE Nucleotide [O] 7 April 2014 (2014-04-07), "Cloning vector pGL3-U6-sgRNA-PG, complete sequence", XP055566618, retrieved from NCBI Database accession no. KJ175229.1
HERQUEL, B. ET AL.: "Transcription Cofactors TRIM24, TRIM28, and TRIM33 Associate to Form Regulatory Complexes that Suppress Murine Hepatocellular Carcinoma", PNAS, vol. 108, no. 20, 2011, pages 8212 - 8217, XP055566603
GREENHALGH, S. N. ET AL.: "Cre-tivity in the Liver: Transgenic Approaches to Targeting Hepatic Nonparenchymal Cells", HEPATOLOG Y, vol. 61, no. 6, 2015, pages 2091 - 2099, XP055566613
DATABASE Nucleotide [O] 7 April 2014 (2014-04-07), "Cloning vector pGL3-U6-sgRNA-PG, complete sequence", XP055566618, retrieved from NCBI Database accession no. KJ175229.1
Attorney, Agent or Firm:
LEE, Myoung-Jin (KR)
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