US 11,788,076 B2
Full replacement technique for T cell receptor using platinum TALEN
Tatsuo Ichinohe, Hiroshima (JP); Takashi Yamamoto, Higashi-Hiroshima (JP); Tetsushi Sakuma, Higashi-Hiroshima (JP); Yasuko Honjo, Hiroshima (JP); Takakazu Kawase, Hiroshima (JP); Takahiko Miyama, Hiroshima (JP); and Ryuji Suzuki, Ibaraki (JP)
Assigned to Hiroshima University, Higashi-Hiroshima (JP); and Repertoire Genesis Incorporation, Ibaraki (JP)
Appl. No. 16/755,074
Filed by Hiroshima University, Higashi-Hiroshima (JP); and Repertoire Genesis Incorporation, Ibaraki (JP)
PCT Filed Oct. 9, 2018, PCT No. PCT/JP2018/037590
§ 371(c)(1), (2) Date Apr. 9, 2020,
PCT Pub. No. WO2019/073964, PCT Pub. Date Apr. 18, 2019.
Claims priority of application No. 2017-197010 (JP), filed on Oct. 10, 2017; and application No. 2018-167954 (JP), filed on Sep. 7, 2018.
Prior Publication US 2020/0362323 A1, Nov. 19, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 9/22 (2006.01); C12N 15/64 (2006.01); C07K 19/00 (2006.01)
CPC C12N 9/22 (2013.01) [C12N 15/64 (2013.01); C07K 19/00 (2013.01); C07K 2319/81 (2013.01)] 5 Claims
 
1. A method of editing a T cell receptor (TCR) gene, comprising introducing into a T cell a composition comprising a nucleic acid encoding a polypeptide comprising a DNA binding domain and a functional domain, wherein
the DNA binding domain and the functional domain are connected by a polypeptide consisting of 35 to 55 amino acids,
the DNA binding domain comprises a plurality of DNA binding modules consecutively from the N-terminal side of the DNA binding domain,
a combination of the xth amino acid and the yth amino acid in the 4n-3th DNA binding module from the N-terminus being identical for any n,
a combination of the xth amino acid and the yth amino acid in the 4n-2th DNA binding module from the N-terminus being identical for any n,
a combination of the xth amino acid and the yth amino acid in the 4n-1th DNA binding module from the N-terminus being identical for any n, and
a combination of the xth amino acid and the yth amino acid in the 4nth DNA binding module from the N-terminus being identical for any n,
the combination of the xth amino acid and the yth amino acid in the 4n-3th DNA binding module from the N-terminus, the combination of the xth amino acid and the yth amino acid in the 4n-2th DNA binding module from the N-terminus, the combination of the xth amino acid and the yth amino acid in the 4n-1th DNA binding module from the N-terminus, and the combination of the xth amino acid and the yth amino acid in the 4nth DNA binding module from the N-terminus are different from one another, and
n is a natural number from 1 to 10, x is a natural number from 1 to 40, y is a natural number from 1 to 40, and x and y are different natural numbers, wherein the functional domain is a DNA cleaving domain, wherein the editing of a TCR gene is removal of an endogenous TCR gene, and wherein the DNA binding domain comprises the amino acid sequence of SEQ ID NO: 86, the amino acid sequence of SEQ ID NO: 87, the amino acid sequence of SEQ ID NO: 88, the amino acid sequence of SEQ ID NO: 89, the amino acid sequence of SEQ ID NO: 90, or the amino acid sequence of SEQ ID NO: 91.