Received: 29 June, 2007. Accepted: 21 August, 2007. Invited Review Advances in Gene, Molecular and Cell Therapy ©2007 Global Science Books Emerging Gene and Cell-Based Therapies and Their Prospects for the Treatment of Animal Diseases Lucía Alonso-González • Stefan Wagner • Götz Laible * Reproductive Technologies, AgResearch, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand Corresponding author: * goetz.laible@agresearch.co.nz ABSTRACT Animal diseases caused by pathogens such as viruses, bacteria and nematodes account for major losses in livestock production and can have dramatic socioeconomic consequences in agriculture-dependant countries. Moreover, in recent years, the unpredictable worldwide outbreaks of pandemic infections such as mad-cow disease and bird flu, and the risks that these diseases pose for the human population, have raised public awareness about the importance of developing strategies for their treatment. The rapid development that cell and molecular genetics has experienced in the past 25 years has provided scientists with powerful new weapons which, unlike the more traditional medical approaches, can directly target the underlying molecular causes of disease. In this review, we will outline the most recent advances in cell and gene therapy applied to the treatment of animal diseases, with a particular focus on livestock animals. Relevant examples have been used to illustrate these novel treatment options and current restrictions, and future prospects for their application to combat animal diseases will be discussed. _____________________________________________________________________________________________________________ Keywords: animal diseases, DNA vaccines, gene therapy, somatic cell nuclear transfer, transgenic animals Abbreviations: BHV-1, bovine herpesvirus 1; BSE, bovine spongiform encephalopathy; BTV, bluetongue virus; BVDV, bovine viral diarrhoea virus; CRA, conditionally replicative adenoviruses; ES cells, embryonic stem cells; FDA, Food and Drug Administration; FE, facial eczema; FMDV, foot and mouth disease virus; HAC, human artificial chromosome; HAT, human African trypanosomiasis; HR, homologous recombination; IHNV, infectious haematopoietic necrosis virus; MAC, mammalian artificial chromosome; MHC, major histocompability complex; PrP, prion protein; QTL, quantitative trait loci; RNAi, RNA interference; SCC, somatic cell counts; shRNA, small hairpin RNA; SLE, systemic lupus erythematosus; SCNT, somatic nuclear cell transfer; SIT, sterile insect technique; SMT, sperm- mediated transgenesis; SPAG, sporozoite surface antigen; VHSV, viral haemorrhagic septicaemia virus; VSV, vesicular stomatitis virus; VWD, Von Willebrand disease; ZFN, zinc finger nuclease CONTENTS INTRODUCTION...................................................................................................................................................................................... 172 ENGINEERING ANIMAL GENOMES FOR DISEASE RESISTANCE.................................................................................................. 174 Transmissible spongiform encephalopathies ......................................................................................................................................... 174 Mastitis .................................................................................................................................................................................................. 175 Facial eczema ........................................................................................................................................................................................ 175 Viral Infections ...................................................................................................................................................................................... 175 COMBINING GENE TECHNOLOGY AND VACCINATION: REVOLUTION OF A SUCCESSFUL STRATEGY ............................. 176 Recombinant vaccines ........................................................................................................................................................................... 176 Nucleic acid vaccines ............................................................................................................................................................................ 176 Plant vaccines ........................................................................................................................................................................................ 178 APPLICATION OF GENE TECHNOLOGY TO COUNTERACT INTERNAL PARASITES ................................................................. 178 CARING FOR THE INDIVIDUAL – TREATMENT OF NON-INFECTIOUS DISEASES .................................................................... 179 PERSPECTIVE.......................................................................................................................................................................................... 181 ACKNOWLEDGEMENTS ....................................................................................................................................................................... 182 REFERENCES........................................................................................................................................................................................... 183 _____________________________________________________________________________________________________________ INTRODUCTION Since the early domestication of animals, men and livestock have developed a mutual dependence; the human became not only the collector of the products domesticated animals provided, but also the guardian of their wellbeing in ex- change for a better and sustainable food supply. Thus, even today, any disease severely affecting livestock will nega- tively impact on society as a whole. Infectious and parasitic diseases which adversely affect livestock have a major impact both upon production, animal welfare and human health (see Table 1). While a drop in quantity might be just an economic burden, in particular for food animals, any compromise in the quality of the food produced poses a significant health risk, which is reflected in the general premise that only healthy animals produce safe food. Furthermore, at least some of the animal diseases as bovine spongiform encephalopathies (BSE) (Will et al. 1996) or avian influenza (Koopmans et al. 2004) also have the potential to transfer to humans. The costs of existing endemic diseases are estimated to account for 17% of the turnover of the livestock industries in the developed world, and up to 50% in developing coun- tries (Whitelaw and Sang 2005). The resulting economic