Animal models for prenatal gene therapy: choosing the right model

Testing in animal models is an essential requirement during development of prenatal gene therapy for -clinical application. Some information can be derived from cell lines or cultured fetal cells, such as the efficiency of gene transfer and the vector dose that might be required. Fetal tissues can also be maintained in culture for short periods of time and transduced ex vivo. Ultimately, however, the use of animals is unavoidable since in vivo experiments allow the length and level of transgene expression to be measured, and provide an assessment of the effect of the delivery procedure and the gene therapy on fetal and neonatal development. The choice of animal model is determined by the nature of the disease and characteristics of the animal, such as its size, lifespan, and immunology, the number of fetuses and their development, parturition, and the length of gestation and the placentation. The availability of a disease model is also critical. In this chapter, we discuss the various animal models that can be used and consider how their characteristics can affect the results obtained. The projection to human application and the regulatory hurdles are also presented.