Protocol

Prenatal Gene Therapy

Volume 891 of the series Methods in Molecular Biology pp 183-200

Date:

Animal Models for Prenatal Gene Therapy: Choosing the Right Model

  • Vedanta MehtaAffiliated withPrenatal Cell and Gene Therapy Group, EGA Institute for Women’s Health, University College London
  • , Donald PeeblesAffiliated withPrenatal Cell and Gene Therapy Group, EGA Institute for Women’s Health, University College London
  • , Anna L. DavidAffiliated withPrenatal Cell and Gene Therapy Group, EGA Institute for Women’s Health, University College London Email author 

* Final gross prices may vary according to local VAT.

Get Access

Abstract

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.

Key words

Disease models Fetal size Fetal growth Fetal development Gestation length Lifespan Fetal immunity Immune responses Gene therapy Vectors Gene transfer Gene expression Fetal number Parturition Preterm birth Placenta Placentation Prenatal diagnosis