# US 11,432,537 B2 · Method for producing blood chimeric animal

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- Number: US 11,432,537 B2
- Document ID: US11432537B2
- Status: Granted
- Kind: B2
- Application number: 15/739,059
- Filed: 2016-06-20
- Published: 2018-06-28
- Granted: 2022-09-06
- Earliest claimed: 2015-06-22
- Assignees: The University of Tokyo; National Federation of Agricultural Coopertive Associations
- Applicants: National Federation of Agricultural Cooperative Associations; The University of Tokyo
- Inventors: Kazuo Fukawa; Tetsuya Ito; Mai Kamikawa; Yutaka Sendai; Hiromitsu Nakauchi; Satoshi Yamazaki; Motoo Watanabe
- Web page: https://patentgrep.com/patent/US11432537B2

## CPC

- A01K 67/0271: Chimeric vertebrates, e.g. comprising exogenous cells
- A01K 67/027: New or modified breeds of vertebrates
- C12N 5/0647: {Haematopoietic stem cells; Uncommitted or multipotent progenitors}
- C12N 15/09: Recombinant DNA-technology
- A01K 2207/12: Animals modified by administration of exogenous cells
- A01K 2217/052: inducing gain of function
- A01K 2227/108: Swine
- A01K 2267/025: Animal producing cells or organs for transplantation
- C12N 2510/00: Genetically modified cells
- C12N 2510/02: Cells for production
- C12N 2517/02: Cells from transgenic animals
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention discloses a novel means capable of producing a blood chimeric animal in which a state of retaining blood cells originating in a heterologous animal at a high percentage is sustained for a long period of time. The method for producing a non-human animal that retains blood cells originating in a heterologous animal, according to the present invention, comprises transplanting hematopoietic cells of a heterologous animal into a non-human animal, in which hematopoietic cells the function of a gene that acts on the hematopoietic system is modified, The gene that acts on the hematopoietic system is, for example, Lnk gene, When a medium to large mammal is used as a recipient, the survival rate of hematopoietic cells originating in a heterologous animal is dramatically increased such that blood chimerism of 10% or more can be maintained even in a 16 month old animal.

## Claims

### Claim 1

A non-human animal that retains blood cells originating in a heterologous animal, in which the hematopoietic cells originating in the heterologous animal survive, said hematopoietic cells being cells in which a function of Lnk gene is inhibited, and which retains the blood cells originating in the heterologous animal in the circulating blood and has a chimerism of nucleated blood cells of 10% or more at the age of 3 months old or at a time point 3 months after the transplantation of the hematopoietic cells, wherein the heterologous animal is of a species different from the non-human animal, wherein said non-human animal is a pig, and wherein the heterologous animal is a mammal.

### Claim 2 (depends on 1)

The non-human animal according to claim 1, wherein the hematopoietic cells comprise hematopoietic stem cells.

### Claim 3 (depends on 1)

The non-human animal according to claim 1, wherein said chimerism of nucleated blood cells is 12% or more.

### Claim 4 (depends on 1)

The non-human animal according to claim 1, wherein said chimerism of nucleated blood cells is 15% or more.

### Claim 5 (depends on 1)

A method for producing blood cells, the method comprising collecting blood from the non-human animal according to claim 1, and separating the blood cells originating in the heterologous animal.