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Production of pharmaceutical proteins in milk

  • Multi-author Review
  • Transgenic vertebrates
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Abstract

There is every reason to expect that it will be possible within the next few years to begin to use farm animals to produce large quantities of some of the human proteins that are needed for the treatment of disease. Revolutionary new opportunities for the production of novel proteins in milk have been created by the development of methods for gene transfer. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue specific hormonally induced expression in the mammary gland. Studies with three genes, ovine β-lactoglobulin, rat β-casein and whey acidic protein of rat and mouse, suggest that they may all meet this requirement. Fragments of the ovine β-lactoglobulin, murine whey acidic protein and rabbit β-casein genes have directed production of novel proteins in the milk of transgenic mice, sheep, rabbits and pigs. The proteins were biologically active and usually co-migrated with authentic proteins. In early experiments, protein concentration was low, but our recent observations suggest that fusion genes containing genomic clones direct production of concentrations of protein that are suitable for commercial exploitation. In the longer term, two approaches may offer the potential of more reliable expression. Control elements capable of directing expression that is independent of site of insertion of the gene, but dependent on the number of copies of the gene, have been identified for a small number of genes. The availability of such elements for the milk protein genes would increase the reliability of gene expression considerably. Alternatively, targeted mutation of genes may allow the insertion of coding sequences within an existing gene so avoiding position effects.

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Authors and Affiliations

  1. AFRC Institute of Animal Physiology and Genetics Research, EH25 9PS, Roslin, Midlothian, Scotland

    I. Wilmut, A. L. Archibald, M. McClenaghan, J. P. Simons, C. B. A. Whitelaw & A. J. Clark

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  1. I. Wilmut
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  2. A. L. Archibald
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  3. M. McClenaghan
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  4. J. P. Simons
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  5. C. B. A. Whitelaw
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  6. A. J. Clark
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Wilmut, I., Archibald, A.L., McClenaghan, M. et al. Production of pharmaceutical proteins in milk. Experientia 47, 905–912 (1991). https://doi.org/10.1007/BF01929881

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