Mhc gene group humanized animal
AssigneeTokyo Metropolitan Institute of Medical Science
InventorsTeruhiko SUZUKI, Takahiko HARA
Life of this patent
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Abstract
A vector set including a combination of the following vectors (A), (B), and (D) or (C) and (D): (A) a targeting vector 1 incorporated at any position P1 distal to a human MHC region, (B) a targeting vector 2 incorporated at a position p1 corresponding to the P1 of a non-human MHC region, (C) a targeting vector 3 that triggers a recombination between a region from the P1 to the distal end and a region from the p1 to the distal end, and (D) a targeting vector 4 that triggers in the chromosome after recombination a recombination between a region from any position P2 proximal to a human MHC region to the distal end and a region from a position p2 corresponding to the P2 in a chromosome in which a non-human MHC is present to the distal end.
Claims33
A vector set comprising a combination of the following targeting vectors (A), (B) and (D), or a combination of the following targeting vectors (C) and (D):
- (A) a targeting vector 1 that is incorporated into human chromosome 6 at an arbitrary position P1 located on the distal side from a major histocompatibility complex (human MHC) region on the short arm of the human chromosome 6,
- wherein the targeting vector 1 causes translocational recombination between a region extending from the aforementioned P1 to the distal end and a region on a non-human mammalian chromosome, the region extending from position p1, which corresponds to the aforementioned P1 and is located on the distal side from a MHC (non-human MHC) region existing on the non-human mammalian chromosome, to the distal end, and the targeting vector 1 also contains a gene cassette 1 containing a recombinase recognition sequence, one partial sequence of a drug resistance gene 1 for drug selection, which is reconstituted upon the translocational recombination, and a drug resistance gene 2 for drug selection after targeting;
- (B) a targeting vector 2 that is incorporated into the non-human mammalian chromosome in which the MHC region exists, at position p1 that corresponds to the aforementioned P1 and that is located on the distal side from the MHC (non-human MHC) region,
- wherein the targeting vector 2 causes translocational recombination between the region extending from the aforementioned p1 to the distal end and the region extending from the aforementioned P1 to the distal end on the human chromosome 6, and the targeting vector 2 also contains a gene cassette 2 containing a recombinase recognition sequence, the other sequence of the drug resistance gene 1, and a drug resistance gene 3 for drug selection after targeting;
- (C) a targeting vector 3 that causes translocational recombination between a region on human chromosome 6, the region extending from an arbitrary position P1, which is located on the distal side from a human MHC region and targeted for cleavage by a genome editing tool, to the distal end, and a region on a non-human mammalian chromosome in which MHC exists, the region extending from position p1, which corresponds to the aforementioned P1 and is located on the distal side from the non-human MHC region, to the distal end,
- wherein the targeting vector 3 contains a homologous sequence of the sequence of partial region R1a located between the aforementioned P1 and the human MHC region, a drug resistance gene 4 for drug selection after targeting, and a homologous sequence of the sequence of partial region R2b located on the distal side from the aforementioned p1, or the targeting vector 3 contains a homologous sequence of the sequence of partial region R1b located on the distal side from the aforementioned P1, a drug resistance gene 4 for drug selection after targeting, and a homologous sequence of the sequence of partial region R2a located between the aforementioned p1 and the non-human MHC region;
- and
- (D) a targeting vector 4 that causes translocational recombination between a region extending from an arbitrary position P2, which is located on the proximal side from the human MHC region and targeted for cleavage by a genome editing tool, to the distal end and a region on the non-human mammalian chromosome in which the non-human MHC exists, the region extending from position p2, which corresponds to the aforementioned P2 and located on the proximal side from the non-human MHC region, to the distal end,
- wherein the targeting vector 4 contains a homologous sequence of the sequence of partial region R3a located on the proximal side from the aforementioned P2, a drug resistance gene 5 for drug selection after targeting, and a homologous sequence of the sequence of partial region R4b located between the aforementioned p2 and the non-human MHC region, or the targeting vector 4 contains a homologous sequence of the sequence of partial region R3b located between the aforementioned p2 and the human MHC region, a drug resistance gene 5 for drug selection after targeting, and a homologous sequence of the sequence of partial region R4a located on the proximal side from the aforementioned p2.
Dependencies are inferred from the claim text.