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Purified plasma derived human albumin has been available as a therapeutic product since World War II. However, cost effective recombinant production of albumin has been challenging due to the amount needed and the complex folding pattern of the protein. In an effort to provide an abundant source of recombinant albumin, a herd of transgenic cows expressing high levels of rhA in their milk was generated. Expression cassettes efficiently targeting the secretion of human albumin to the lactating mammary gland were obtained and tested in transgenic mice. A high expressing transgene was transfected in primary bovine cell lines to produce karyoplasts for use in a somatic cell nuclear transfer program. Founder transgenic cows were produced from four independent cell lines. Expression levels varying from 1-2 g/l to more than 40 g/l of correctly folded albumin were observed. The animals expressing the highest levels of rhA exhibited shortened lactation whereas cows yielding 1-2 g/l had normal milk production. This herd of transgenic cattle is an easily scalable and well characterized source of rhA for biomedical uses.

Research over the past two decades has increased the quality and quantity of tools available to produce genetically engineered animals. The number of potentially viable biomedical products from genetically engineered animals is increasing. However, moving from cutting-edge research to development and commercialisation of a biomedical product that is useful and wanted by the public has significant challenges. Even early stage development of genetically engineered animal applications requires consideration of many steps, including quality assurance and quality control, risk management, gap analysis, founder animal establishment, cell banking, sourcing of animals and animal-derived material, animal facilities, product collection facilities and processing facilities. These steps are complicated and expensive. Biomedical applications of genetically engineered animals have had some recent successes and many applications are well into development. As researchers consider applications for their findings, having a realistic understanding of the steps involved in the development and commercialisation of a product, produced in genetically engineered animals, is useful in determining the risk of genetic modification to the animal v. the potential public benefit of the application.

The role of viruses in the etiology of recurrent upper respiratory disease in newly weaned lambs was studied during 1984–1985 at the North Dakota Sheep Experiment Station. Serum samples collected from lambs at weaning, from lambs with signs of respiratory disease, and 3 weeks following the onset of clinical signs were tested for antibodies to ovine adenovirus (OAV), respiratory syncytial virus (RSV), and Parainfluenza type-3 virus (PI-3). Virus isolation studies were performed on nasal secretions samples taken at the same time. Parainfluenza type-3 was isolated from 1 of 275 lambs tested, and there was 2.5% overall 4-fold increase in antibody titer to PI-3 during the 2-year study. An adenovirus with a different restriction endonuclease digestion pattern from that of previously reported adenovirus strains in the United States was isolated from 13 of 275 nasal secretions collected from lambs at the time of weaning. There was a 17.6% overall 4-fold increase in seroconversion to the adenovirus isolated from the lambs with clinical disease.

Bovine oocytes derived from abattoir origin are mainly used for artificial reproductive techniques in both agricultural and biomedical applications. Regulatory agencies have expressed concern for potential transmission of adventitious viruses by sourcing bovine oocytes from abattoir origin. To evaluate this concern, a viral risk assessment was conducted on batch samples collected from follicular fluid, cumulus cells, oocytes, and Day 8 embryos. These batch samples were collected from ovaries on seven randomly selected days in a 2-week period and they were frozen and stored at –80°C until tested. All samples were tested by 9 Code of Federal Regulations (9CFR) part 113.53c (animal viral testing) at a GLP compliant laboratory (American BioResearch Laboratories, Sevier, TN, USA). The 9CFR viral testing includes bovine viral diarrhea virus (BVDV), bovine parvovirus, bovine adenovirus type 3 and 5, bovine rabies virus, bovine bluetongue virus, bovine respiratory syncytial virus, bovine reovirus, viral cytopathic effect, and hemadsorption on permissive cell cultures. Batch samples were also tested for BVDV and bovine leukemia virus (BLV) by polymerase chain reaction (PCR) and follicular fluids for BVDV antibody neutralization activity at an accredited diagnostic laboratory (Animal Disease Research and Diagnostic Laboratory, SDSU, Brookings, SD, USA). The 9CFR viral testing results on all the batch samples were negative. The BVDV PCR test had a low positive (37.89 cycles) with one follicular fluid batch sample (1/7) and a low positive (37.9 cycles) on all cleaved embryos (7/7). However, BVDV virus isolation was negative for both batch samples by 9CFR testing. The BLV PCR had a positive follicular batch sample (1/7), with all other samples testing being negative. BVD serum neutralization antibody assay demonstrated that all follicular fluid had significant titers of 1:128–1:1024. Although some of the viral particles may have been detected in follicular fluid and cleaved embryos by PCR, none of the batch samples collected were positive for viral growth in this study. The BVDV PCR indicated low levels of BVDV RNA. It is speculated that the positive BVDV PCR results on cleaved embryos could possibly be attributed to the use of irradiated fetal calf serum (contaminated BVDV virus) used in culture media. Follicular fluids also have high titers to BVDV which may have neutralized the virus. These results indicate that virus-free bovine oocytes can be derived from the abattoir. Thus, with appropriately applied quality assurance testing, abattoir-origin oocytes might be used effectively in agricultural and biomedical applications. Table 1. Summary of test results on batch samples from abattoir-derived oocytes