title: Dolly, Polly and other 'ollys': likely impact of cloning technology on biomedical uses of livestock.
abstract: The idea of generating transgenic livestock which secrete into their milk large quantities of proteins for therapeutic use, was pioneered in the late 1980s with the disclosure of the production of a number of transgenic sheep. One particular animal, a sheep called Tracy, produced milk where over 50% of the protein consisted of human alpha 1 anti-trypsin. Sheep-derived protein has now entered clinical trials for cystic fibrosis (UK, USA) and congenital emphysema (UK). There are many other examples where this technology is making inroads into more traditional ways of making biopharmaceuticals. However, although robust, this technology has several limitations, including an inability to allow targeted insertion/modification of the animal genome, long timelines to production flocks/herds, and the rather unpredictable expression levels seen when different transgenic founders are compared. We believe that there is now a technical solution to all of these problems. Dolly is a high profile example of a new technology comprising the generation of identical animals from cultured somatic cells. This work has many implications. In the commercial context, the real benefits of this advance will be seen when genetically engineered somatic cells are shown to be suitable nuclear donors, and particularly when the manipulations are targeted to pre-determined sites in the host cell genome. The first objective has now been achieved with the birth of Polly, a cloned sheep which contains the human gene encoding Factor IX, a protein involved in preventing haemophilia.
authors.affiliation: PPL Therapeutics, Roslin, Edinburgh, UK. acolman@ppl-therapeutics.com
authors.forename: A
authors.initials: A
authors.lastname: Colman
mesh_terms: D000822:Animal Husbandry / Q000379:methods*; D000818:Animals; D030801:Animals, Genetically Modified; D001688:Biological Products / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use; D001709:Biotechnology / Q000379:methods*; D002417:Cattle; D002986:Clinical Trials as Topic; D019976:Cloning, Organism / Q000379:methods; D004992:Ethics, Medical; D005164:Factor IX / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D016332:Fetal Tissue Transplantation; D005818:Genetic Engineering; D005822:Genetic Vectors; D006041:Goats; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism; D008845:Microinjections; D008894:Milk Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D053652:Nuclear Transfer Techniques; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use; D012756:Sheep / Q000235:genetics; D016662:Virus Integration; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use
chemical_list: D001688:Biological Products; D008894:Milk Proteins; D011994:Recombinant Proteins; D000515:alpha 1-Antitrypsin; D005164:Factor IX