inflammatory responses do occur when viral gene therapy is used (Thomas et al., 2001). The most common viruses utilized as gene therapy vectors are lentiviruses (Quinonez and Sutton, 2002), herpes simplex viruses (Burton et al., 2002), adenoviruses (Lai et al., 2002), and adeno-associated viruses (Lai et al., 2002). However, newer generations of viral vectors seem to provoke less serious immune responses (Anonymous, 1996).

Stem cells have also been shown to cause an adverse immune response. This immune response is termed graft-versus-host disease and can occur acutely or chronically in a large percentage of patients (Abo-Zena and Horwitz, 2002). Clinical signs of an immune reaction depend on the species of animal, the type of reaction, and the organs affected. The reactions may result in local or systemic symptoms, including such vague symptoms as fever, vomiting, diarrhea, ataxia, and behavior changes and such dramatic symptoms as anaphylactic shock (Aiello, 1998c) or degeneration of the target organ (Yang et al., 1994). Many times immunosuppressive drugs or irradiation is used in combination with stem cell therapies. These can have significant adverse consequences on an animal’s health and well-being, including causing opportunistic infections and cancers due to the immune suppression (Junghanss and Marr, 2002).

Gene therapy also has the potential to be tumorigenic (Donsante et al., 2001) and stem cells have tumorigenic tendencies (Le Belle and Svendsen, 2002; Ruiz et al., 2002). Stem cell transplantation into the brain has also been shown to result in hyperplasia and atypical integration (Zheng et al., 2002). As a result, animals that undergo stem cell or gene therapy should be monitored acutely for immune reactions and chronically for tumor development and neurological dysfunction caused by hyperplasia or atypical integration. A plan for monitoring expected and unexpected consequences should be developed (see Chapter 3).

Occupational Health and Safety

The potential for unexpected consequences of gene therapy extends to the potential for infection of researchers, animal-care technicians, and other laboratory-animal species with the recombinant DNA under investigation. To manage the potential risks, NIH produced Guidelines for Research Involving Recombinant DNA Molecules (NIH, 1998). That document identified which kinds of experiments involving recombinant DNA required institutional biosafety committee approval or notification. Some of the designated experiments include research involving transgenic rodents and the use of infectious DNA or RNA viruses. Appendix Q of the document identifies the physical and biologic containment requirements for handling animals involved in recombinant-DNA research.

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