TARGETED REPLACEMENT OF ENDOGENOUS T CELL RECEPTORS

Japanese Patent JP2022137112

A

To provide methods of editing the genome of a human T cell.SOLUTION: The present disclosure provides a method of editing the genome of a human T cell, the method comprising inserting a nucleic acid sequence into a target region in exon 1 of a T cell receptor (TCR)-subunit constant gene in the human T cell, a nucleic acid sequence encoding from a N-terminus to a C-terminus, (i) a first self-cleaving peptide sequence; (ii) a first heterologous TCR subunit chain comprising the variable region and the constant region of the TCR subunit; (iii) a second self-cleaving peptide sequence; (iv) a variable region of a second heterologous TCR subunit chain; and (v) a portion of the N-terminus of the endogenous TCR subunit, wherein, if the endogenous TCR subunit is TCR-α, the first subunit is TCR-β, and the second subunit is TCR-α, and wherein if the endogenous TCR subunit is TCR-β, the first is TCR-α, and the second is TCR-β.SELECTED DRAWING: Figure 1a

Los Theodore Lee
Sifult Eric
Marson Alexander
Puig South Christina
Rivas Antoni

JP2022103225A

September 21, 2022

June 28, 2022

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The Regents of the University of California

C12N15/09; A61K35/17; A61K48/00; A61P35/00; C12N5/10

WO2017106528A2	2017-06-22
WO2014153470A2	2014-09-25

PNAS, vol. 112, JPN6021048863, 2015, pages 10437 - 10442, ISSN: 0005100589
NATURE, vol. 543, JPN6021048865, 2 March 2021 (2021-03-02), pages 113 - 117, ISSN: 0005100590

Shimizu Hatsushi
Masao Haruna
Hirotaka Yamaguchi
Shun Jinbe
Ryuichi Inoue
Toshimitsu Sato
Koichi Niimi
Tomohiko Kobayashi
Hideki Kodera
Masato Ozeki
Kazuya Kawamoto

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