The use of transgenic animals in the production of pharmaceuticals has opened an innovative field of study bringing medicine to the barnyard. A transgenic animal is modified to contain genetic information from another organism, and animals have been designed to produce pharmaceutical human proteins. While the prospects are promising, the future use of transgenic animals in pharmaceutics necessitates a careful consideration of the ethics and efficiency of protein production.
The production of human proteins has been a road ridden with pitfalls and muddy slopes, indicating the need to explore alternative methods. The endeavor to produce these proteins using blood and tissue extracts is inefficient, demanding time and money in addition to the risk of contamination by human pathogens . Using genetically engineered bacteria also poses problems due to the high cost and limited quantity of production . Furthermore, bacteria cannot effectively synthesize some proteins, especially more complex ones, nor perform the proper post-translational modifications of proteins produced [1, 2]. Improper post-translational modifications result in unfavorable immune reactions in the patients . While genetically engineered mammalian cell cultures resolve the problem of performing post-translational modifications, difficulties arise in the purification of the proteins . Because of the shortcomings of the various methods of pharmaceutical protein production, there is a considerable need to investigate alternatives for said production.
The use of transgenic animals has become an attractive means of protein production because it addresses the challenges found in existing methods of production. The mammary glands of transgenic animals serve as a target site for protein production because of the capability to produce large quantities of proteins that are then comparatively easy to extract and purify . Additional benefits include proper post-translational modifications of the proteins, cost-efficient production, and the stability of the genetic expression of the animals that allows them to produce proteins . These advantages provide a strong case to further investigate the use of transgenic animals in pharmaceutical protein production.
Currently, the proteins produced by transgenic animals have a variety of potential applications in the treatment of human diseases. For instance, the human coagulations factor VIII (FVIII) and factor IX (FIX) for the treatment of the hereditary blood coagulation disease hemophilia have been produced in the milk of transgenic pigs [4, 5]. Moreover, transgenic animals have been used to produce the von Willebrand factor, which is involved in blood coagulation, to treat von Willebrand disease . A testament to their versatility, transgenic animals are not limited to the production of coagulation proteins. The repertoire of potential products from transgenic animals includes monoclonal antibodies, hormones, growth factors, enzymes, and vaccines .
However, toying with nature by creating transgenic animals may result in unforeseen repercussions, regardless of the good intentions, and raises ethical questions. Studies show that genetically modifying animals does not pose complications in breeding , but other potential effects on the animals are still under investigation. For instance, genetically modifying rabbits to produce human erythropoietin, a hormone involved in the production of red blood cells, was found to harm the health of the animals . While investigating the potential of using transgenic animals in protein production inevitably involves the sacrifice of some animals, measures to ensure the well-being of the animals involved is not only necessary for the effective production of proteins but also an ethical responsibility. The health of the offspring of transgenic animals is also in question. Because of the potential benefits of using transgenic animals in pharmaceutical protein production, pursuing further research in this field is worthwhile but necessitates precaution. The Food and Drug Administration (FDA) of the United States has already set guidelines concerning the verification of the proper genetic modification in transgenic animals and the condition of the animals, as well as their progeny . Other guidelines address the breeding of transgenic animals and the purification of the products found in the milk . Prudence should guide the active investigation of the using transgenic animals in pharmaceutical protein production.
In addition to the need to address ethical concerns, the future of transgenic animals in pharmaceutics requires refining the efficiency of production. While the production costs are low and the quality of the proteins high, some difficulties in separating the human proteins from the animal matter still persist . Improving the purification process is essential to future use of transgenic animal in pharmaceutics. Additionally, the ability to stably represent the genetic modification in transgenic animals and successfully pass the modification to healthy offspring will improve the cost-efficiency of the process. Optimizing the concentration of proteins in the milk is also necessary. Studies show that a concentration of 1 milligram per milliliter of milk or lower is an effective level to produce quality proteins . Continued efforts to improve the efficiency of protein production are critical.
Considering the potential benefits and the current research, the future of transgenic animals in pharmaceutics is promising. While the mammary glands have been targeted as a protein production site, scientists have explored alternatives. In addition to milk, chicken egg whites have become a promising alternative vehicle for the production of human proteins . The use of transgenic animals in pharmaceutics can become a viable industry, demonstrated by the predicted increase in number of companies involved in this means of producing pharmaceutical human proteins . The corresponding increase in competition will instigate further research, and it is through this continued research and innovation that the use of transgenic animals will become a favorable means of producing pharmaceuticals.
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- Houdebine LM. Production of pharmaceutical proteins by transgenic animals. Comp Immunol Microbiol Infect Dis. 2009 Mar; 32(2): 107-21. Epub 2008 Feb 19.
- Wells DJ. Genetically modified animals and pharmacological research. In: Cunningham F, Elliott J, Lees P, editors. Comparative and Veterinary Pharmacology [e-book]. Berlin: Springer; 2010 [cited 2010 July 7]. Available from: SpringerLink. http://www.springerlink.com/content/g101911788411236/.
- Paleyanda RK, Velander WH, Lee TK, Scandella DH, Gwazdauskas FC, Knight JW, et al. Transgenic pigs produce functional human factor VIII in milk. Nat Biotechnol. 1997 Oct; 15(10): 971-5.
- Gil GC, Velander WH, Van Cott KE. Analysis of the N-glycans of recombinant human Factor IX purified from transgenic pig milk. Glycobiology. 2008 Jul; 18(7): 526-39. Epub 2008 May 2.
- Lee HG, Lee HC, Kim SW, Lee P, Chung HJ, Lee YK, et al. Production of recombinant human von Willebrand factor in the milk of transgenic pigs. J Reprod Dev. 2009 Oct; 55(5): 484-90. Epub 2009 Jun 11.