Related Experiment Videos
Rhesus monkey model for fetal gene transfer: studies with retroviral- based vector systems
A F Tarantal1, J P O'Rourke, S S Case
1California Regional Primate Research Center, University of California at Davis, 95616-8542, USA. aftarantal@primate.ucdavis.edu
Summary
This study shows that fetal gene therapy in rhesus monkeys is safe and efficient, with lentiviral vectors achieving the highest gene transfer to hematopoietic progenitors for potential in utero treatments.
Area of Science:
- Reproductive Medicine
- Genetics
- Primate Research
Background:
- In utero gene therapy offers potential for treating congenital diseases.
- Fetal rhesus monkeys serve as a valuable preclinical model for human gene transfer studies.
Purpose of the Study:
- To evaluate the efficiency and safety of in utero gene transfer using different viral vectors in fetal rhesus monkeys.
- To compare gene transfer rates to various tissues and hematopoietic progenitors.
Main Methods:
- Viral vectors (MLV-based, VSV-G pseudotyped MLV, lentiviral) expressing EGFP were administered to fetal rhesus monkeys via intraperitoneal or intrahepatic routes.
- Fetal and postnatal specimens were analyzed using PCR and fluorescence microscopy.
- Tissue harvests were performed at birth or 3-6 months post-gene transfer.
Main Results:
- Lentiviral vectors demonstrated significantly higher gene transfer to hematopoietic progenitors (approx. 25%) compared to MLV-based vectors (4-9%).
- Gene transfer was observed in multiple organ systems, with detectable EGFP in peripheral blood, thymus, liver, spleen, lymph nodes, brain, and bone marrow.
- No evidence of transplacental transfer of vector sequences to the dams was detected.
Conclusions:
- Fetal administration of retroviral vectors in primates leads to widespread gene transfer to multiple organ systems.
- Lentiviral vector systems show superior efficiency for gene transfer to hematopoietic progenitors in fetal primates.
- The rhesus monkey model is suitable for preclinical evaluation of in utero gene therapy approaches for human applications.