Title: Tissue modificationField of inventionThis invention concerns selective modification of tissues of animals.
Summary of the inventionAccording 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.