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Production of pharmaceutical proteins by transgenic animals.
Comp Immunol Microbiol Infect Dis. 2009 Mar; 32(2):107-21.CI

Abstract

Proteins started being used as pharmaceuticals in the 1920s with insulin extracted from pig pancreas. In the early 1980s, human insulin was prepared in recombinant bacteria and it is now used by all patients suffering from diabetes. Several other proteins and particularly human growth hormone are also prepared from bacteria. This success was limited by the fact that bacteria cannot synthesize complex proteins such as monoclonal antibodies or coagulation blood factors which must be matured by post-translational modifications to be active or stable in vivo. These modifications include mainly folding, cleavage, subunit association, gamma-carboxylation and glycosylation. They can be fully achieved only in mammalian cells which can be cultured in fermentors at an industrial scale or used in living animals. Several transgenic animal species can produce recombinant proteins but presently two systems started being implemented. The first is milk from farm transgenic mammals which has been studied for 20 years and which allowed a protein, human antithrombin III, to receive the agreement from EMEA (European Agency for the Evaluation of Medicinal Products) to be put on the market in 2006. The second system is chicken egg white which recently became more attractive after essential improvement of the methods used to generate transgenic birds. Two monoclonal antibodies and human interferon-beta 1a could be recovered from chicken egg white. A broad variety of recombinant proteins were produced experimentally by these systems and a few others. This includes monoclonal antibodies, vaccines, blood factors, hormones, growth factors, cytokines, enzymes, milk proteins, collagen, fibrinogen and others. Although these tools have not yet been optimized and are still being improved, a new era in the production of recombinant pharmaceutical proteins was initiated in 1987 and became a reality in 2006. In the present review, the efficiency of the different animal systems to produce pharmaceutical proteins are described and compared to others including plants and micro-organisms.

Authors+Show Affiliations

Biologie du Développement et Reproduction, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France. louis.houdebine@jouy.inra.fr

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18243312

Citation

Houdebine, Louis-Marie. "Production of Pharmaceutical Proteins By Transgenic Animals." Comparative Immunology, Microbiology and Infectious Diseases, vol. 32, no. 2, 2009, pp. 107-21.
Houdebine LM. Production of pharmaceutical proteins by transgenic animals. Comp Immunol Microbiol Infect Dis. 2009;32(2):107-21.
Houdebine, L. M. (2009). Production of pharmaceutical proteins by transgenic animals. Comparative Immunology, Microbiology and Infectious Diseases, 32(2), 107-21. https://doi.org/10.1016/j.cimid.2007.11.005
Houdebine LM. Production of Pharmaceutical Proteins By Transgenic Animals. Comp Immunol Microbiol Infect Dis. 2009;32(2):107-21. PubMed PMID: 18243312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Production of pharmaceutical proteins by transgenic animals. A1 - Houdebine,Louis-Marie, Y1 - 2008/02/19/ PY - 2007/11/10/accepted PY - 2008/2/5/pubmed PY - 2009/4/15/medline PY - 2008/2/5/entrez SP - 107 EP - 21 JF - Comparative immunology, microbiology and infectious diseases JO - Comp. Immunol. Microbiol. Infect. Dis. VL - 32 IS - 2 N2 - Proteins started being used as pharmaceuticals in the 1920s with insulin extracted from pig pancreas. In the early 1980s, human insulin was prepared in recombinant bacteria and it is now used by all patients suffering from diabetes. Several other proteins and particularly human growth hormone are also prepared from bacteria. This success was limited by the fact that bacteria cannot synthesize complex proteins such as monoclonal antibodies or coagulation blood factors which must be matured by post-translational modifications to be active or stable in vivo. These modifications include mainly folding, cleavage, subunit association, gamma-carboxylation and glycosylation. They can be fully achieved only in mammalian cells which can be cultured in fermentors at an industrial scale or used in living animals. Several transgenic animal species can produce recombinant proteins but presently two systems started being implemented. The first is milk from farm transgenic mammals which has been studied for 20 years and which allowed a protein, human antithrombin III, to receive the agreement from EMEA (European Agency for the Evaluation of Medicinal Products) to be put on the market in 2006. The second system is chicken egg white which recently became more attractive after essential improvement of the methods used to generate transgenic birds. Two monoclonal antibodies and human interferon-beta 1a could be recovered from chicken egg white. A broad variety of recombinant proteins were produced experimentally by these systems and a few others. This includes monoclonal antibodies, vaccines, blood factors, hormones, growth factors, cytokines, enzymes, milk proteins, collagen, fibrinogen and others. Although these tools have not yet been optimized and are still being improved, a new era in the production of recombinant pharmaceutical proteins was initiated in 1987 and became a reality in 2006. In the present review, the efficiency of the different animal systems to produce pharmaceutical proteins are described and compared to others including plants and micro-organisms. SN - 1878-1667 UR - https://www.unboundmedicine.com/medline/citation/18243312/Production_of_pharmaceutical_proteins_by_transgenic_animals_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0147-9571(07)00130-0 DB - PRIME DP - Unbound Medicine ER -