Targeted introduction of DNA into primary or secondary cells and their use for gene therapy and protein production

A method of providing a therapeutic product in an effective amount to a mammal comprising the steps of:

• a) providing a DNA construct comprising:
• 1) exogenous DNA encoding a product to be expressed in primary or secondary cells of mammalian origin;
• 2) DNA sequences homologous with genomic DNA sequences in the primary or secondary cells of mammalian origin;
• and
• 3) DNA sequences encoding at least one selectable marker;
• b) transfecting primary or secondary cells obtained from a mammal with the DNA construct provided in (a), thereby producing primary or secondary cells containing the DNA construct provided in (a);
• c) maintaining primary or secondary cells produced in (b) under conditions appropriate for homologous recombination to occur between DNA sequences homologous with genomic DNA sequences and genomic DNA sequences,
• thereby producing homologously recombinant primary or secondary cells of mammalian origin having the DNA construct of (a) integrated into genomic DNA of the primary or secondary cells;
• and
• d) introducing said homologously recombinant primary or secondary cells produced in (c) into a mammal in sufficient number to produce an effective amount of the therapeutic product in the mammal,
• wherein said recombinant primary or secondary cells are from the same species as said mammal.