# US 11,849,709 B2 · Genetically modified rat models for severe combined immunodeficiency (SCID)

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- Number: US 11,849,709 B2
- Document ID: US11849709B2
- Status: Granted
- Kind: B2
- Application number: 17/553,463
- Filed: 2021-12-16
- Published: 2022-06-02
- Granted: 2023-12-26
- Earliest claimed: 2009-07-01
- Assignees: Hera Testing Laboratories, Inc.
- Applicants: Hera Testing Laboratories, Inc.
- Inventors: Eric M. Ostertag; John Stuart Crawford; Joseph Ruiz
- Web page: https://patentgrep.com/patent/US11849709B2

## CPC

- A01K 67/0276: Knock-out vertebrates
- C12N 9/1205: {Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases}
- C12N 9/14: Hydrolases (3)
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- C12N 15/87: Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N 15/907: {in mammalian cells}
- A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic)
- A01K 2217/054: inducing loss of function
- A01K 2217/056: due to mutation of coding region of the transgene (dominant negative)
- A01K 2217/15: Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
- A01K 2217/20: Animal model comprising regulated expression system
- A01K 2217/206: Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
- A01K 2227/105: Murine
- A01K 2267/0331: Animal model for proliferative diseases
- A01K 2267/0387: Animal model for diseases of the immune system
- C12N 2015/8536: {Animal models for genetic diseases}
- 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

This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

## Claims

### Claim 1

A genetically engineered rat, or progeny of the rat, whose genome comprises a homozygous knock-out of the interleukin 2 receptor subunit gamma (Il2rg) gene and a homozygous knock-out of the recombination activating gene 1 (Rag 1) gene, wherein the rat or its progeny exhibits Severe Combined Immunodeficiency (SCID), wherein the rat or its progeny has decreased levels of mature T-cells, B-cells and NK-cells, as compared to a rat not comprising the knock-out of the Il2rg gene and the knock-out of the Rag1 gene.

### Claim 2 (depends on 1)

The genetically engineered rat, or progeny of the rat, of claim 1, wherein the rat or its progeny lacks mature B-cells, T-cells, and NK-cells.

### Claim 3 (depends on 1)

The genetically engineered rat, or progeny of the rat, of claim 1 wherein the rat or its progeny is capable of accepting a xenograft without eliciting an immune response.

### Claim 4 (depends on 3)

The genetically engineered rat, or progeny of the rat, of claim 3, wherein the xenograft is a tumor xenograft or healthy tissue xenograft.

### Claim 5 (depends on 3)

The genetically engineered rat, or progeny of the rat, of claim 3, wherein the xenograft is from human lymphoid or myeloid tissues.

### Claim 6 (depends on 3)

The genetically engineered rat, or progeny of the rat, of claim 3, wherein the xenograft is from human peripheral blood lymphocytes.

### Claim 7 (depends on 3)

The genetically engineered rat, or progeny of the rat, of claim 3, wherein the xenograft is from human thymus.

### Claim 8 (depends on 3)

The genetically engineered rat, or progeny of the rat, of claim 3, wherein the xenograft is from human liver tissue.

### Claim 9 (depends on 1)

The genetically engineered rat, or progeny of the rat, of claim 1, wherein the rat or its progeny comprises a xenograft.

### Claim 10 (depends on 9)

The genetically engineered rat, or progeny of the rat, of claim 9, wherein the xenograft is a tumor xenograft or healthy tissue xenograft.

### Claim 11 (depends on 9)

The genetically engineered rat, or progeny of the rat, of claim 9, wherein the xenograft is from human lymphoid or myeloid tissues.

### Claim 12 (depends on 9)

The genetically engineered rat, or progeny of the rat, of claim 9, wherein the xenograft is from human peripheral blood lymphocytes.

### Claim 13 (depends on 9)

The genetically engineered rat, or progeny of the rat, of claim 9, wherein the xenograft is from human thymus.

### Claim 14 (depends on 9)

The genetically engineered rat, or progeny of the rat, of claim 9, wherein the xenograft is from human liver tissue.

### Claim 15 (depends on 1)

The genetically engineered rat, or progeny of the rat, of claim 1, wherein the rat or its progeny comprises transplanted cells.

### Claim 16 (depends on 15)

The genetically engineered rat, or progeny of the rat, of claim 15, wherein the transplanted cells comprise human cells.

### Claim 17 (depends on 15)

The genetically engineered rat, or progeny of the rat, of claim 15, wherein the transplanted cells comprise human hepatic cells.

### Claim 18 (depends on 15)

The genetically engineered rat, or progeny of the rat, of claim 15, wherein the transplanted cells comprise primary cells, secondary cells, or a combination thereof.

### Claim 19 (depends on 18)

The genetically engineered rat, or progeny of the rat, of claim 18, wherein the primary cells comprise primary cells from healthy subjects, or primary cells from subjects with genetic lesions associated with disease states.

### Claim 20 (depends on 15)

The genetically engineered rat, or progeny of the rat, of claim 15, wherein the transplanted cells comprise stem cells.

### Claim 21 (depends on 20)

The genetically engineered rat, or progeny of the rat, of claim 20, wherein the stem cells comprise embryonic cells, hematopoietic stem cells, amniotic cells, umbilical cord cells, mesenchymal stem cells, hepatic cells, adipose stromal cells, or induced pluripotent cells.