1. ¹California National Primate Research Center, University of California, Davis, CA 95616, USA
2. ²Department of Pediatrics, University of California, Davis, Davis, CA 95616, USA
3. ³Department of Obstetrics and Gynecology, University of California, Davis, Davis, CA 95616, USA
4. ⁴Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA
5. ⁵Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA

Correspondence: Alice F. Tarantal, California National Primate Research Center, University of California, Davis, Pedrick and Hutchison Roads, Davis, CA 95616, USA. Fax: +1 (530) 752 2880. E-mail: aftarantal@primate.ucdavis.edu.

Received 21 February 2004; Accepted 26 January 2005.

Abstract

Fetal gene transfer was studied using intrapulmonary and intramyocardial transfer of SIN HIV-1-derived lentiviral vectors expressing EGFP in rhesus monkeys. Fetuses were monitored sonographically during gestation and tissue analyses performed at term or 3 months postnatal age. Animals remained healthy during the study period as evidenced by normal growth, development, hematology, clinical chemistry, echocardiography, and pulmonary function tests. Strong pulmonary fluorescence was observed postnatally after fetal intrapulmonary delivery of lenti-CMV, but not lenti-SP-C, and compared to nontransferred controls. High EGFP copy numbers were found by quantitative PCR with both vector constructs in lung lobes (15%) and EGFP copies were also detected in the diaphragm, pericardium, and thorax. No differences were found in lung:body weight ratios, percentage lung parenchyma, or overall morphology when compared to controls. For intramyocardial gene delivery, strong transgene expression was found within the myocardium and pericardium, and high EGFP copy numbers were found by quantitative PCR (3–36%). EGFP was also detected in the aorta, thorax, and diaphragm. These studies indicate that postnatal heart and lung development and function were not altered after fetal intraorgan gene transfer and subsequent transgene expression prenatally and postnatally, and gene transfer was restricted to the thoracic cavity with intrapulmonary and intramyocardial lentiviral vector-mediated gene delivery.