Recombinant technologies in micro-organisms being used to produce commercial and medically useful proteins like insulin are fairly common.

However some proteins are still produced commercially in genetically modified animals. Why are animals a better choice than microorganisms, and which are the most common proteins produced this way?

  • $\begingroup$ Transgenic animals are not used for commercial activities as of now. $\endgroup$
    Commented May 19, 2013 at 19:49

2 Answers 2


ATryn is a human antithrombin produced in the milk of transgenic goats by GTC Biotherapeutics. It has FDA approval and I believe that it is available for prescription in the USA.

Added later, after the emphasis of the question changed somewhat.

Proteins produced in a mammalian system are more likely to have post-translational modifications that are much closer to those found on the human protein. Antithrombin, for example, has four disulphide bonds and four glycosylation sites. Although it is reasonable to assume that the disulphide bonds would be correctly formed in a eukaryotic microorganism, the same isn't true of the glycosylation: microbial glycans differ from mammalian glycans, and these differences could affect the stability of the protein in the mammalian bloodstream, or the response of the mammalian immune system to the protein. Mammalian cells in culture could be used but are, of course, quite fastidious. So the holy grail of recombinant protein production has always been to get the protein secreted into an animal's milk, allowing the use of very cheap feedstocks and the easy harvest of the protein over a period of years, notwithstanding @shigeta's remarks.

  • $\begingroup$ might well be right that this is the only current case. Transgenic animals are really expensive compared to transgenic bacteria - its very expensive to make a transgenic goat and the ability to produce the transgenic product often doesn't breed through - making you start all over again from scratch when the goats die. $\endgroup$
    – shigeta
    Commented May 24, 2013 at 3:56

The rationale for the choice of higher organisms as the producing source is based on costs and biological activity.

  • Biological activity. In their active forms, various proteins have post-translational modifications (i.e. glycosylation) which are difficult to reproduce in bacteria. Alan's answer is already exhaustive.
  • Costs. Mammalian cell lines are easier to generate and maintain but suffer from genetic and epigenetic instability (the transgene can be lost or inactivated). Contrarywise, transgenic animals require more investment but once established that the transgene is present in the germline and breed through, the protein can be produced in larger quantities with ~1/10 of the costs required to setup a GMP-bioreactor. This is particularly appealing for small pharmaceutical niches, i.e. drugs targeting rare diseases: if the market is small, farming few goats can be more profitable than building and maintaining sterile bioreactors. Downstream purification facilities are however required for both cellular and animal farms. That's why animal models that produce high levels of the therapeutic protein in secreted matrices (i.e. milk, egg white) are preferred: this facilitates bulk storage of unpurified protein prior to purification.

    A good and recent review comparing models and strategies is from Wang et al., Expression Systems and Species Used for Transgenic Animal Bioreactors (doi:10.1155/2013/580463).

To stay updated on recombinant proteins from transgenic farms entering the market, the official reference would probably be the FDA section on Biologics. Two companies actively working on transgenic farms are GTC Biotherapeutics and Synageva.

  • GTC Biotherapeutics produces human antithrombin alfa (ATryn) in the milk of transgenic goats, for use in patients with hereditary antithrombin deficiency (HD). Quoting the ATryn executive report:

    Antithrombin III (recombinant) is a highly purified, well characterized recombinant glycoprotein consisting of432 amino acids, 3 disulphide bridges between cysteine residues and 4-N linked glycosylation sites, identical to human plasma-derived antithrombin. Recombinant human antithrombin is produced in the milk of transgenic goats. For expression of rhAT, the DNA construct contained a goat beta casein promoter with the cDNA coding region for human antithrombin (hAT). The DNA construct was microinjected into fertilized one-cell goat embryos, which were transFerred to female recipients. Kids born from the recipients were tested for presence of the transgene and expression of the human protein. A founder transgenic goat was selected from which subsequent offspring were generated by natural breeding to give rise to a production herd of hAT transgenic goats, which are milked to provide the source material for downstream purification.

  • Synageva produces Sebelipase alfa (SBC-102) in the egg white of transgenic hens, for use as an enzyme replacement for Lysosomal Acid Lipase (LAL) Deficiency. I think they are in clinical phase 2/3 (not yet on the market). According to their 2012 Annual Report:

    Our proprietary vectors allow incorporation of the gene of interest into the genome of normal cells of an avian (Gallus) with selective expression of the resulting protein in the oviduct tissues and secretion into EW. The importance of this cellular environment for therapeutic protein expression is highlighted by the tight consistency of post-translational modification, including glycosylation, seen in proteins manufactured using our platform compared to cell culture produced material. Furthermore, our expression system yields consistent expression levels and quality of protein within production lines and through multiple generations.


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