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3. FRONTIERS AND ADVANCES IN TRANSGENIC
BIOTECHNOLOGY OF ANIMALS AND FISHES
INTRODUCTION
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Dr. Shao-Yang Hu
Dr. Jen-Leih Wu
Institute of Cellular and Organismic Biology
Academia Sinica
Taipei, Republic of China
Transgenic technology has become widely applied worldwide since the creation of transgenic
mice in 1987 to produce tissue plasminogen activator (tPA). Various transgenic animals
carrying segments of foreign DNA have been genetically engineered in diverse research areas,
such as in providing developmental models for drug testing, xenotransplantation, and the production
of pharmaceutical proteins. Furthermore, in 1997, the successful cloning of “Dolly” the
sheep attracted the concern of media and society about transgenic technology, and animal
cloning became a topic of intense discussion. Transgenic farm animals represent an attractive
system for efficient production of large, complex, and biologically active recombinant proteins.
A large number of useful proteins have been successfully expressed in sheep, goats, pigs, and
cattle, and several recombinant proteins are now in clinical trials. However, because of the threat
of variant Creutsfeldt-Jacob disease (CDJ) and other human and animal virus infections, fishes
may provide an alternative animal system for transgenic application and research. Since the first
transgenic fish were successfully produced in 1985 (Zhu et al., 1985), gene transfer studies have
been conducted in over 35 important fish species for aquaculture.
According to a report published by Business Communication Company Inc. (BCC), the
pharmaceutical market worldwide was over USD33 billion in 2003 and is predicted to be more
than USD60 billion in 2006. This shows that the biotechnology industry has a high potential for
growth. Currently, the major topics in transgenic animal and fish research include improving the
quality of bioproducts, use as animal models for human disease research, use as a bioreactor for
the production of pharmaceutical recombinant protein or additional nutrient food, and as a
source of organs to be used in xenotransplantation. This paper will describe the current status of
transgenic animals and fish, genetically modified for commercial use. In addition to a brief
review of the application of transgenic animals, the content will focus on the advancement of
transgenic fish.
ADVANCES IN DEVELOPING TRANSGENIC ANIMALS
Commercial production of bioproducts using natural protein factories such as the mammary
glands of dairy animals has been a goal of animal scientists since the first report of a transgenic
mouse (Gordon and Ruddle, 1981). This method of production is frequently referred to as biopharming.
The conventional production of rare human therapeutic proteins from blood or tissue
extracts is an inefficient, expensive, and time-consuming process. Prokaryotic expression systems
are only suited for simple proteins, and post-translational modifications are often incorrect,
leading to immune reactions against the protein. Therefore, farm animals such as cattle, sheep,
goats, and pigs provide several advantages for production of recombinant proteins, including
their potential for large-scale production, post-translational modifications, and correct structure.
To date, large amounts of numerous heterologous recombinant proteins—including pharmaceutical
proteins, vaccine, and various antibodies—have been produced by expression in mammary
glands through mammary-gland-specific promoters (Table 1).