GB2223755A - Tissue modification - Google Patents
Tissue modification Download PDFInfo
- Publication number
- GB2223755A GB2223755A GB8822157A GB8822157A GB2223755A GB 2223755 A GB2223755 A GB 2223755A GB 8822157 A GB8822157 A GB 8822157A GB 8822157 A GB8822157 A GB 8822157A GB 2223755 A GB2223755 A GB 2223755A
- Authority
- GB
- United Kingdom
- Prior art keywords
- tissue
- animal
- dna
- selected tissue
- polypeptide product
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000012986 modification Methods 0.000 title description 3
- 230000004048 modification Effects 0.000 title description 3
- 210000001519 tissue Anatomy 0.000 claims abstract description 32
- 241001465754 Metazoa Species 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 18
- 210000005075 mammary gland Anatomy 0.000 claims abstract description 6
- 229920001184 polypeptide Polymers 0.000 claims abstract description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 6
- 239000000463 material Substances 0.000 claims abstract description 5
- 239000002243 precursor Substances 0.000 claims abstract description 4
- 210000004185 liver Anatomy 0.000 claims abstract description 3
- 210000003079 salivary gland Anatomy 0.000 claims abstract description 3
- 210000003491 skin Anatomy 0.000 claims abstract description 3
- 230000000392 somatic effect Effects 0.000 claims abstract description 3
- 230000000366 juvenile effect Effects 0.000 abstract description 2
- 230000003248 secreting effect Effects 0.000 abstract description 2
- 108020004414 DNA Proteins 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- -1 factors VIII and IX Chemical compound 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Environmental Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Biophysics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
There is provided a method of selectively modifying a tissue of an animal, comprising introducing foreign DNA directly to the selected tissue or to material that will develop into the selected tissue, to produce localised somatic transgenesis of the tissue. The method may be applied to a developing foetus, with DNA introduced to a precursor of the selected tissue, or to a new born animal, or a juvenile animal or possibly even a mature adult animal. Suitable target tissues include the mammary gland, skin, liver and salivary gland. By introducing DNA the method can be used to endow the selected tissue with particular properties, with the tissue expressing the introduced DNA and typically producing and secreting a desired polypeptide product.
Description
Title: Tissue modification
Field of invention
This invention concerns selective modification of tissues of animals.
Summary of the invention
According to one aspect of the present invention there is provided a method of selectively modifying a tissue of an animal, comprising introducing foreign DNA directly to the selected tissue or to material that will develop into the selected tissue, to produce localised somatic transgenesis of the tissue.
The method may be applied to a developing foetus, with DNA introduced to a precursor of the selected tissue, to a newborn animal, a juvenile animal or possibly even a mature adult animal.
Suitable target tissues include the mammary gland, skin, liver and the salivary gland.
The DNA can be introduced by any suitable technique, such as techniques known for introducing DNA into cells in culture. These include: 1 Use of a retrivoval vector carrying the DNA of interest, introduced to an appropriate location. This is a very efficient technique in terms of the number of cells transformed.
2 Use of calcium phosphate solution with the DNA of interest, introduced to an appropriate location, resulting in integration of the DNA with cells.
3 Use of electroporation, in which DNA of interest introduced to an appropriate location is exposed to an electric field resulting in fusion of the DNA with cells.
Details of the technique will depend on the stage of development of the animal and the target tissue. For example, when dealing with a foetus it is necessary to identify and treat the precursor of the selected target tissue. Thus if the target tissue is, say, the mammary gland treatment should be targetted to the breast epithelial bud of the foetus, which will develop into the mammary epithelium of one teat of the eventual animal.
Suitable material, eg a retrovival vector etc, can be introduced to the identified location of the developing foetus in situ, eg by injection.
By introducing suitable DNA the method can be used to endow the selected tissue with particular properties, with the tissue expressing the introduced DNA and typically producing and secreting a desired polypeptide product.
The product may act to improve properties of the tissue, eg endowing tissue selective disease resistence, say by production of an antibiotic to keep down infections.
Alternatively the product may be harvested from the animal, eg by being recovered from milk if produced in the mammary gland, with the animal being used as a convenient 'factory' for production of the product. This approach can provide a useful source of pure materials, free from infectious agents such as those causing AIDS or hepatitis, and is particularly valuable for the production of medically useful proteins such as insulin, blood coagulation factors such as factors VIII and IX, blood proteins such as beta-globin, plasminogen activator, serum proteins such as alphal-antitrypsin and so on.
The invention may be applied to any animal of interest but it is envisaged it will be applied particularly to domestic animals such as cattle, sheep, pigs and goats and laboratory animals such as mice and rats.
In a further aspect the present invention provides an animal treated by the method of the invention.
Yet another aspect of the invention provides a polypeptide product recovered from a tissue of an animal treated by the method of invention.
The approach of the present invention is to be contrasted with prior proposals which involve incorporation of DNA into the germ line, for example as disclosed in W088/00239 of Pharmaceutical Proteins Ltd. This specification describes incorporation, preferably in vitro, of a DNA sequence coding for a polypeptide into a gene of a mammal coding for a milk whey protein in such a way that the DNA sequence is expressed in the mammary gland of the adult female mammal.
Claims (6)
1. A method of selectively modifying a tissue of an animal, comprising introducing foreign DNA directly to the selected tissue or to material that will develop into the selected tissue, to produce localised somatic transgenesis of the tissue.
2. The method of claim 1 applied to a developing foetus, with DNA introduced to a precursor of the selected tissue.
3. The method of claim 1 or 2 in which the target tissue is selected from the mammary gland, skin, liver and the salivary gland.
4. The method of any preceding claim wherein the tissue expresses the introduced DN and produces and secretes a desired polypeptide product.
5. An animal treated by the method of any preceding claim.
6. A polypeptide product recovered from a tissue a of an animal treated by the method by any of claims 1 to 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8822157A GB2223755A (en) | 1988-09-21 | 1988-09-21 | Tissue modification |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8822157A GB2223755A (en) | 1988-09-21 | 1988-09-21 | Tissue modification |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB8822157D0 GB8822157D0 (en) | 1988-10-26 |
| GB2223755A true GB2223755A (en) | 1990-04-18 |
Family
ID=10643982
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8822157A Withdrawn GB2223755A (en) | 1988-09-21 | 1988-09-21 | Tissue modification |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2223755A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991002056A1 (en) * | 1989-08-09 | 1991-02-21 | Transgene S.A. | Cell lineages expressing a biologically active ix factor |
| EP0625007A1 (en) * | 1992-01-27 | 1994-11-23 | North Carolina State University | Gene transfer in birds by introduction of dna into muscle in ovo |
| WO1995009011A1 (en) * | 1993-09-30 | 1995-04-06 | University Of Pennsylvania | Methods of stimulating phagocytosis |
| US5780009A (en) * | 1995-01-20 | 1998-07-14 | Nexia Biotechnologies, Inc. | Direct gene transfer into the ruminant mammary gland |
| US5856178A (en) * | 1993-08-30 | 1999-01-05 | Utah State University | DNA cassettes for expression of lytic peptides in mammalian cells and transgenic organisms containing same |
| US6297048B1 (en) | 1992-02-04 | 2001-10-02 | Chiron Corporation | Hepatitis therapeutics |
| US6515199B1 (en) | 1992-01-27 | 2003-02-04 | North Carolina State University | Gene transfer in poultry by introduction of embryo cells in ovo |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988010304A1 (en) * | 1987-06-16 | 1988-12-29 | Edison Animal Biotechnology Center | Dietary and hormonal regulation of expression of exogenous genes in transgenic animals under control of the promoter of the gene for phosphoenolpyruvate carboxykinase |
| EP0169672B1 (en) * | 1984-06-22 | 1992-05-13 | The President And Fellows Of Harvard College | Method for producing transgenic animals |
-
1988
- 1988-09-21 GB GB8822157A patent/GB2223755A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0169672B1 (en) * | 1984-06-22 | 1992-05-13 | The President And Fellows Of Harvard College | Method for producing transgenic animals |
| WO1988010304A1 (en) * | 1987-06-16 | 1988-12-29 | Edison Animal Biotechnology Center | Dietary and hormonal regulation of expression of exogenous genes in transgenic animals under control of the promoter of the gene for phosphoenolpyruvate carboxykinase |
Non-Patent Citations (1)
| Title |
|---|
| Nature 1986, 323, 445-44 * |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991002056A1 (en) * | 1989-08-09 | 1991-02-21 | Transgene S.A. | Cell lineages expressing a biologically active ix factor |
| EP0625007A1 (en) * | 1992-01-27 | 1994-11-23 | North Carolina State University | Gene transfer in birds by introduction of dna into muscle in ovo |
| US6515199B1 (en) | 1992-01-27 | 2003-02-04 | North Carolina State University | Gene transfer in poultry by introduction of embryo cells in ovo |
| EP0625007A4 (en) * | 1992-01-27 | 1997-02-26 | Univ North Carolina State | Gene transfer in birds by introduction of dna into muscle in ovo. |
| US6395961B1 (en) | 1992-01-27 | 2002-05-28 | North Carolina State University | Gene transfer in chickens by introduction of DNA into muscle in ovo |
| US6297048B1 (en) | 1992-02-04 | 2001-10-02 | Chiron Corporation | Hepatitis therapeutics |
| US5856178A (en) * | 1993-08-30 | 1999-01-05 | Utah State University | DNA cassettes for expression of lytic peptides in mammalian cells and transgenic organisms containing same |
| US5821071A (en) * | 1993-09-30 | 1998-10-13 | University Of Pennsylvania | Methods of stimulating phagocytosis |
| US6068983A (en) * | 1993-09-30 | 2000-05-30 | University Of Pennsylvania | Methods of stimulating phagocytosis |
| US5776910A (en) * | 1993-09-30 | 1998-07-07 | University Of Pennsylvania | Methods of stimulating phagocytosis |
| US6475997B1 (en) | 1993-09-30 | 2002-11-05 | University Of Pennsylvania | Methods of stimulating phagocytosis |
| WO1995009011A1 (en) * | 1993-09-30 | 1995-04-06 | University Of Pennsylvania | Methods of stimulating phagocytosis |
| US5780009A (en) * | 1995-01-20 | 1998-07-14 | Nexia Biotechnologies, Inc. | Direct gene transfer into the ruminant mammary gland |
Also Published As
| Publication number | Publication date |
|---|---|
| GB8822157D0 (en) | 1988-10-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 732 | Registration of transactions, instruments or events in the register (sect. 32/1977) | ||
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |