Successful expression of β-galactosidase and factor IX transgenes in fetal and neonatal sheep after ultrasound-guided percutaneous adenovirus vector administration into the umbilical vein

Themis M, Schneider H, Kiserud T, Cook T, Adebakin S, Jezzard S, Forbes SJ, Hanson M, Pavirani A, Rodeck C, Coutelle C (1999)

Publication Language: English

Publication Type: Journal article, Original article

Publication year: 1999

Journal

Gene Therapy Nature Publishing Group: Open Access Hybrid Model Option B

Book Volume: 6

Pages Range: 1239-1248

Journal Issue: 7

DOI: 10.1038/sj.gt.3300970

Abstract

In utero somatic gene therapy in the later stages of pregnancy may allow targeting of organ systems which are difficult to reach later in life and to prevent the development of tissue damage otherwise caused by the early onset of inherited diseases. We report here on the percutaneous delivery of two adenoviral vectors, containing the β-galactosidase reporter gene and the human Factor IX gene respectively, to the fetal liver and circulation by ultrasound-guided umbilical vein puncture similar to procedures used in human pregnancy. Vector spread, as detected by PCR analysis for the β-galactosidase encoding vector, was found in almost all fetal and neonatal organs and in the maternal liver. Expression of the β-galactosidase transgene was detected in many fetal tissues by RT-PCR. High β-galactosidase production was shown by immuno-histochemistry predominantly in the liver, where about 30% of the hepatocytes stained positive, and in the adrenal cortex. Production of factor IX was determined by ELISA in the plasma of treated fetuses and newborn lambs and reached at birth up to 80% of the normal human plasma concentration. This demonstrates a very hopeful proof of principle for the development of prenatal treatment of many genetic diseases but also requires more detailed investigations with respect to the observed systemic spread of the vector.

Authors with CRIS profile

Holm Schneider

Involved external institutions

University of Edinburgh GB United Kingdom (GB) Imperial College London / The Imperial College of Science, Technology and Medicine GB United Kingdom (GB)

How to cite

APA:

Themis, M., Schneider, H., Kiserud, T., Cook, T., Adebakin, S., Jezzard, S.,... Coutelle, C. (1999). Successful expression of β-galactosidase and factor IX transgenes in fetal and neonatal sheep after ultrasound-guided percutaneous adenovirus vector administration into the umbilical vein. Gene Therapy, 6(7), 1239-1248. https://doi.org/10.1038/sj.gt.3300970

MLA:

Themis, Mike, et al. "Successful expression of β-galactosidase and factor IX transgenes in fetal and neonatal sheep after ultrasound-guided percutaneous adenovirus vector administration into the umbilical vein." Gene Therapy 6.7 (1999): 1239-1248.

BibTeX: Download