Fetal Muscle Gene Therapy/Gene Delivery in Large Animals
Gene delivery to the fetal muscles is a potential strategy for the early treatment of muscular dystrophies. In utero muscle gene therapy can also be used to treat other genetic disorders such as hemophilia, where the missing clotting proteins may be secreted from the treated muscle. In the past few years, studies in small animal models have raised the hopes that a phenotypic cure can be obtained after fetal application of gene therapy. Studies of efficacy and safety in large animals are, however, essential before clinical application can be considered in the human fetus. For this reason, the development of clinically applicable strategies for the delivery of gene therapy to the fetal muscles is of prime importance. In this chapter, we describe the protocols for in utero ultrasound-guided gene delivery to the ovine fetal muscle in early gestation. In particular, procedures to inject skeletal muscle groups such as the thigh and thoracic musculature and targeting the diaphragm in the fetus are described in detail.
Key wordsFetus Fetal gene therapy Prenatal therapy Gene therapy Sheep Ultrasound Intramuscular Intrapleural Intraperitoneal Muscle
- 26.Themis M, Schneider H, Kiserud T, Cook T, Adebakin S, Jezzard S et al. (1999) Successful expression of b-galactosidase and factor IX transgenes in fetal and neonatal sheep after ultrasound-guided percutaneous adenovirus vector administration into the umbilical vein. Gene Ther 6, 1239–1248.PubMedCrossRefGoogle Scholar
- 27.David AL, Peebles DM, Gregory L, Waddington SN, Themis M, Weisz B et al. (2006) Clinically applicable procedure for gene delivery to fetal gut by ultrasound-guided gastric injection: toward prenatal prevention of early-onset intestinal diseases. Hum Gene Ther 17, 767–779.PubMedCrossRefGoogle Scholar