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Transgenic bioreactors
Affiliation:1. Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland;2. Department of Signal Transduction, Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany;3. Ligandis GbR, Dorfstr. 14, 18276 Gülzow-Prüzen, Germany;4. Medical Research Laboratory, Department of Clinical Medicine, Department of Endocrinology & Internal Medicine, University Hospital, 8000 Aarhus C, Denmark;5. Roche Pharma Research and Early Development (pRED), Pharmaceutical Sciences, Global DMPK and Bioanalytical R&D, Roche Innovation Center Munich, Germany
Abstract:
  • 1.1. Although many human therapeutic proteins are currently produced in microbial fermentors using recombinant DNA techniques, it is obvious that microbial processing is not suitable for a large number of bioactive proteins owing to the inability of bacteria to carry out postsynthetic modification reactions required for full biological activity.
  • 2.2. This disadvantage does not apply to animal cell bioreactors that can generate biologically fully active entities, yet the use of large-scale animal cell cultures for production purposes is prohibitively expensive.
  • 3.3. With the advent of transgenic technology, the production of valuable human pharmaceuticals in large farm animals (pig, sheep, goat and dairy cattle) has become more and more attractive as a high-quantity, low-cost alternative. By employing targeted gene transfer, e.g. using mammary gland-specific regulatory sequences fused with the desired production genes, it is possible to govern the expression to occur exclusively in the mammary gland and hence the gene product is being ultimately secreted into the milk.
  • 4.4. While reviewing the remarkable progress in this field that has even led to commercial exploitations, we will outline in somewhat greater detail our strategy for the use of dairy cattle as a bioreactor for valuable proteins of pharmaceutical interest.
Keywords:
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