Commercializing Genetically Engineered Cloned Cattle

The past 25 years or more have witnessed many new technological developments in the production of genetically engineered (GE) animals, including cattle. These new technologies include producing GE animals by somatic cell cloning, zinc finger nuclease (ZFN)- and transcription activator-like effector nuclease (TALEN)-mediated genome engineering, and extensive genetic modification by sequential gene targeting. Using GE animals to address unmet medical needs, such as producing large quantities of fully human therapeutic antibodies in a transchromosomic (Tc) bovine system, has become a reality. There is great potential in using GE animals for biomedical applications. However, while tremendous breakthroughs and technological innovations continue, maneuvering through highly innovative research and development into regulatory approval and commercialization of valuable animal biotechnology products that are needed and wanted by consumers, physicians, and patients is challenging. Many complicated, rigorous, and often expensive steps are required, which should be considered during early stages of developing applications in GE animals. These steps include the sourcing of animals and animal-derived material; detailed documentation of gene targeting constructs; cell banking; founder animal establishment and genetic characterization; animal facilities; product collection and processing facilities; and regulatory compliance, risk management, gap analysis, quality assurance, and quality control. Recent success in biomedical applications using GE animals is evidenced by the approval of the first GE animal derived biotherapeutic by the European Union and the United States. However, compared to the rapid advances in technology development, the successful commercialization of products produced from GE animals has been slow. While many products are well into development, scientists considering commercial applications for their research should have a broad understanding of the requirements for the development and commercialization of GE animals and products thereof. For example, it is important to consider the risk of genetic modification to the animal versus acceptance by the public based on the benefits of the application

A Two-Year Study of Vaccination in the Prevention of Bovine E. Coli Diarrhea

This is a discussion of a two year study on vaccination in the prevention of bovine E. Coli Diarrhea. Investigations have demonstrated many causes of diarrhea in calves, including management and infectious agents (34, 73). The infectious agents presently recognized as the causative agents of diarrhea include many viruses such as rotavirus, IBR and BVD. In addition, bacteria including the Salmonella spp., Clostridium spp., and Escherichia coli (E. coli) have frequently been associated with calf diarrhea (84)

Production of recombinant albumin by a herd of cloned transgenic cattle

Abstract 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