We sought to develop a more direct method for the in vivo transfection of pgcs with minitol2 transposon plasmids to generate stable germline transgenic male chickens capable of passing the transgene onto the next generation. We believe a transgenic chicken system offers a number of advantages over either plant or other transgenic animal systems for protein production. The hens reproductive system has unique characteristics which have imposed limitations on the use of established methods for artificial gene transfer. Recent advances in avian transgenesis have made it theoretically possible to use transgenic chickens as protein bioreactors. Pedigrees of the transgenic progeny of rooster 43 and subsequent generations are shown. Short generation time, appropriate posttranslational modification of newly synthesized proteins as opposed to prokaryotes and yeasts, higher titers of recombinant proteins produces compared to cultured animal cells, and secretion of transgenic biomolecules into sterile egg white or ovalbumin are the features that make poultry as. Researchers in the college of agriculture and life sciences department of poultry science have developed a powerful new tool to aid the understanding of how chicken embryos develop. Chickens have several advantages, including short generation time, egg production, and the easy scaleup of transgenic. In this paper, we compared different systems capable of producing therapeutic proteins bacteria, mammalian cells, transgenic plants, and transgenic animals and found that transgenic animals were potentially ideal bioreactors for the synthesis of pharmaceutical protein complexes. Development of transgenic chickens expressing human. Germ cells and transgenesis in chickens sciencedirect. Production of germline transgenic chickens expressing. Pdf expression systems and species used for transgenic.
Transgenic plant used for production products plants such as tobacco, potato, tomato, banana, legumes, and cereals as well as alfalfa, are used in molecular farming and have emerged as promising biopharming systems for production of pharmaceutical proteins, such as antibodies, vaccines, regulatory proteins and enzymes. Transgenic chickens as bioreactors have several advantages, such as the simple establishment procedure, correct glycosylation profile of expressed proteins, etc. I n most animals, segregation of the germ line from the somatic lineages is one of the earliest events in. The shorter generation time, lower maintenance costs, and the.
Future prospects a number of recent findings may increase the efficiency of producing transgenic farm animals and give us the ability to make precise genetic modifications. Transgenic animals worcester polytechnic institute. All remaining procedures were done following the manufacturers manual. The application of transgenic technology to domestic poultry offers an alternative means to conventional practice for improvement of this highly productive agricultural species. Generation of transgenic chickens expressing the human. The production of recombinant proteins is one of the major successes of. Transgenic chickens represent a useful model system for studies on embryonic development and as a lowcost, highyield bioreactor for efficient production of human proteins of pharmaceutical importance because of their unique reproductive physiology, costeffectiveness, and ease of protein purification chapman et al. The goal of such work is to produce large quantities of recombinant proteins in the milk or plasma of transgenic mammals or in the eggs of transgenic hens. Dna sequencing showed that the transgene had been integrated at chromosome 26 of the g 1 and g 2 generation transgenic chickens. Creating transgenic chickens nw resistance against genetic. The transgenic chicken has been considered as a prospective bioreactor for largescale pro duction of costly pharmaceutical proteins. A transgenic animal has been genetically engineered to incorporate a foreign gene.
Transgenesis in chickens springerlink transgenic research. The development of transgenic chicken technology has lagged far behind that. These animals should eventually prove to be valuable sources of proteins for human therapy. Thus, we demonstrated that transgenic chickens, expressing a human protein under the control of a ubiquitous promoter, not only could be an efficient bioreactor.
In july 2000, researchers from the team that produced dolly reported success in producing transgenic lambs in which the transgene had been inserted at a specific. Transgenic chickens could potentially serve as bioreactors for commercial production of recombinant proteins in egg white. Making recombinant proteins in animals different systems. Transgenic animal bioreactors represent a powerful tool to address the growing need for therapeutic recombinant proteins. Researchers have created genetically modified hens that lay eggs containing high levels of these functional therapeutic proteins in the egg whites, potentially. The use of chicken oviducts as bioreactors was thought to circumvent. Transgenic farm animals may have great value as bioreactors to produce peptide pharmaceuticals at high levels with appropriate posttranscriptional modification. There are significant differences between the reproductive physiology of birds and mammals. A chicken bioreactor for efficient production of functional cytokines. Plants usually mature after one season of growth and it is possible to bring out the product to the market within a. The genetic modification of pigs to improve their suitability as organ donors for xenotransplantation has been initiated, but many challenges remain. Regarding transgenic chickenmediated human cytokine production, the. A chicken bioreactor for efficient production of functional.
Improvements in transgenic technologies allow valuable proteins to be produced by geneticallymodified animals. Oviductspecific expression of two therapeutic proteins in. Recent advances in the efficiency of transgenic technology have important implications for medicine. Feb 01, 2005 transgenic chickens as bioreactors for proteinbased drugs transgenic chickens as bioreactors for proteinbased drugs lillico, simon g mcgrew, michael j sherman, adrian. Transgenic chickens as bioreactors for proteinbased drugs. As a result, genetically modified animals of several species, expressing foreign proteins. Production of transgenic chickens constitutively expressing human. Expression systems and species used for transgenic animal. Conclusions regulation and further research are needed the use of hens as protein bioreactors is a very convenient issue as solve the posttransduction protein modifications plus they are high efficient and relatively cheap protein production how are lentiviral vectors made. Lab animal volume 36, page 8 2007cite this article. Request pdf transgenic chickens as bioreactors for proteinbased drugs the potential of using transgenic animals for the synthesis of therapeutic proteins was suggested over twenty years ago. A transgenic production flock can be built up within a comparatively short period of time. Origen therapeutics president and chief executive officer. This project details transgenic animal technology, applications, ethics and legalities, as an example of technologys impact on society.
Government approves transgenic chicken the eggs of the genetically engineered animal contain an enzyme that can treat a rare disease by rachel becker, nature magazine on december 9, 2015. The chicken is a promising candidate as a bioreactor for the economical mass production of human therapeutic proteins. Government approves transgenic chicken scientific american. Transgenic chickens as bioreactors by sara aljama lopez on prezi. An overview of the basics of generate transgenic hen. Request pdf transgenesis and poultry as bioreactors the birds as live bioreactors have unique advantages. Rooster 43 and hens 5308 and 5657 were bred to non transgenic chickens to obtain hemizygous offspring. Transgenic chickens should be nearperfect bioreactors for making large amounts of pure recombinant proteins, says ann gibbins, an avian biologist at the university of guelph in ontario, who did the pioneering studies in the field and trained many of those. Relative to mammalian transgenic animal bioreactors, a flock of bioreactor chickens is faster and cheaper to produce, and egg white is a simpler mixture of proteins with a significantly lower lipid content than milk. Expression systems and species used for transgenic animal bioreactors article pdf available in biomed research international 20. The hen has long held promise as a lowcost, highyield bioreactor for the production of human biopharmaceuticals in egg whites using genetic engineering. Chickens have lagged behind mammals in bioreactor development, despite a number of potential advantages, due to the historic difficulty in producing transgenic birds, but the production of therapeutic proteins in egg white of transgenic chickens would substantially lower costs across the entire production cycle compared to traditional cell culture. Request pdf transgenic chickens as bioreactors for proteinbased drugs the potential of using transgenic animals for the synthesis of therapeutic proteins.
The use of transgenic chickens as bioreactors to synthesize therapeutic proteins, as a component of egg yolk or white, may have several advantages over mammalian expression systems, including a shorter timescale for setup and ease of scaleup to a transgenic flock, lower. Transgenic animals can be used as disease models, transpharmers, xenotransplanters, food sources, and other biological models. The most exciting of these include diseaseresistant transgenic poultry, genetically. Many transgenic chickens have been generated by randomly integrating. Research in the fields of life science, pharmacology, and biomedical engineering has created a large demand for transgenic animals, which are advantageous for producing experimental model animals, protein production in transgenic bioreactors, and xenotransplantation donors. An animal contains a foreign gene genesintroduced purposely by human interventiontransgenic animals are altered so that their dnaproduce proteins that normally they would notproduce. Poultry scientists develop transgenic chicken to aid study of embryo development. A significant advantage of the use of hens as bioreactors, in comparison with the utilization of cattle, sheep or goats, is the short incubation time of three weeks and the relatively short generation time of. Transgenic plants as bioreactors arun k sharma, dewal jani, c raghunath and akhilesh k tyagi department of plant molecular biology, university of delhi, south campus, new delhi 110021, india recent advances in molecular and cellular biology have led to the development of technology to engineer plants that are capable of producing a wide variety of products. Oviductspecific enhanced green fluorescent protein. The ability of transgenic animals to produce complex, biologically active recombinant proteins in an efficient and economic manner has stimulated a great deal of interest in this area. Owing to the stable integration of the transgene, it is now feasible to produce g 3 generation of homozygous egfp transgenic chickens that will provide 100% transgenic eggs. Transgenic farm animals ilar journal oxford academic.
Progress towards development of chicken bioreactors methods for production of transgenic chickens. The potential of using transgenic animals for the synthesis of therapeutic proteins was suggested over twenty years ago. Considerable progress has been made in developing methods for the production of. Applications of avian transgenesis oxford academic journals. Transgenic animal bioreactors can produce therapeutic proteins with high value for pharmaceutical use.
Transgenesis and poultry as bioreactors request pdf. It is simpler, costeffective and faster to produce transgenic plants as compared to transgenic animals. Chickens were genetically modified to produce a synthetic decoy rna derived from a sequence present in all strains of avian influenza, and which interferes with virus replication. The use of recombinant proteins has increased in diverse commercial sectors. The birds as live bioreactors have unique advantages. Transgenesis and poultry as bioreactors springerlink. Transgenic chickens are now able to synthesize human proteins in the white of their eggs. Various systems for protein production have been used for the optimization of production and functional protein expression. Feb 01, 2005 transgenic chickens as bioreactors for proteinbased drugs.
831 643 1092 916 606 425 54 942 1237 1473 1185 527 641 55 878 687 1225 896 670 1006 401 494 1279 131 1582 230 1546 347 1280 976 1356 1018 836 1067 231