Animal models for prenatal gene therapy: the sheep model

Area of Science:

• Reproductive biology
• Genetics
• Veterinary medicine

Background:

• Large animal models are essential for bridging the gap between small animal studies and human clinical trials in prenatal gene therapy.
• Sheep offer significant advantages as a large animal model due to their physiological similarities to humans and established use in pregnancy research.

Purpose of the Study:

• To outline the essential animal husbandry practices for establishing timed pregnancies in sheep.
• To describe various fetal injection techniques, including minimally invasive and surgical approaches, for prenatal gene therapy research in sheep.

Main Methods:

• Detailed description of sheep husbandry for timed pregnancies.
• Explanation of ultrasound- and fetoscopic-guided fetal injection techniques.
• Description of laparotomy as a surgical alternative for fetal injection.

Main Results:

• Successful generation of time-mated sheep pregnancies suitable for experimental procedures.
• Demonstration of multiple feasible routes for in utero fetal injection in sheep.
• Establishment of sheep as a viable large animal model for prenatal gene therapy research.

Conclusions:

• Sheep are a well-suited large animal model for prenatal gene therapy research, offering translational relevance.
• The described methods facilitate the safe and effective delivery of genetic material to the ovine fetus.
• This work supports the advancement of prenatal gene therapy through robust large animal experimentation.