# US 5,574,206 A · Transgenic mouse carrying a non-infectious HIV genome

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- Number: US 5,574,206 A
- Document ID: US5574206A
- Status: Granted
- Kind: A
- Application number: 08/294,908
- Filed: 1994-08-24
- Granted: 1996-11-12
- Earliest claimed: 1991-05-15
- Assignees: L'Institut de Recherches Cliniques de Montreal
- Inventors: Paul Jolicoeur
- Web page: https://patentgrep.com/patent/US5574206A

## CPC

- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- C07K 14/005: from viruses
- A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic)
- A01K 2227/105: Murine
- A01K 2267/0337: Animal models for infectious diseases
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C12N 2740/12022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2740/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2740/16222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- Y10S 435/948: using viruses or cell lines
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

Disclosed herein is a transgenic mouse carrying a transgene which expresses non-infectious HIV ribonucleic acid, and the complementary proteins thereof. The transgenic mouse is useful as a source for obtaining the complementary proteins, and as an animal model to study HIV host cell interactions and to evaluate anti-HIV drugs.

## Claims

### Claim 1

A transgenic mouse in which the germ cells and somatic cells carry at least one copy of a single transgene that comprises:
(i) a HIV DNA genome from which is deleted the 5'-LTR, a portion of the 5' leader sequence, and a portion of the 3'-LTR, whereby said HIV DNA and its RNA transcript are rendered non-infectious,
(ii) the MMTV LTR promoter operatively linked to the 1' end of said DNA, and
(iii) the SV40 poly(A) addition signal operatively linked to the 3' end of said DNA, wherein said transgene is introduced into said mouse or an ancestor thereof as a single transgene, such that said mouse has the entire coding sequence of said HIV DNA genome, but produces non-infectious HIV RNA, said transgenic mouse further expressing (a) detectable levels of RNA transcripts encoding HIV proteins env, gag and pol in a promoter-specific manner, and (b) detecting levels of HIV structural proteins env and gag.

### Claim 2

A transgenic mouse in which the germ cells and somatic cells carry at least one copy of a single transgene that comprises:
(i) a HIV DNA genome from which is deleted the 5'-LTR, a portion of the 5' leader sequence, and a portion of the 3'-LTR, whereby said HIV DNA and its RNA transcript are rendered non-infectious,
(ii) the NF-L promoter operatively linked to the 5' end of said DNA, and
(iii) the SV40 poly(A) addition signal operatively inked to the 3' end of said DNA, wherein said transgene is introduced into said mouse or an ancestor thereof as a single transgene, such that said mouse has the entire coding sequence of said HIV DNA genome, but produces non-infectious HIV RNA, said transgenic mouse further expressing (a) detectable levels of RNA transcripts encoding HIV proteins env, gag and pol in a promoter-specific manner, and (b) detectable levels of HIV structural protein gag in spinal cord and brain tissues.

### Claim 3 (depends on 1, 2)

A method for producing a transgenic mouse of claims 1 or 2, comprising:
(a) isolating a fertilized oocyte from a first female mouse,
(b) transferring the transgene recited in claims 1 or 2 into the fertilized oocyte;
(c) transferring a fertilized oocyte containing the transgene to the uterus of a second female mouse;
(d) maintaining said second female mouse such that:
(i) said second female mouse becomes pregnant with the embryo derived from said fertilized oocyte containing the transgene,
(ii) said embryo develops into said transgenic mouse, and
(iii) said transgenic mouse is viably born from said second female mouse; wherein the transgenic mouse has the genetic sequence for non-infectious HIV-1 proviral DNA and is capable of being bred to produce offspring having cells stably containing said genetic sequence.