Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/7320
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | In utero injection of a-L-iduronidase-carrying retrovirus in canine mucopolysaccharidosis type I: Infection of multiple tissues and neonatal gene expression |
Author: | Meertens, L. Zhao, Y. Rosic-Kablar, S. Li, L. Chan, K. Dobson, H. Gartley, C. Lutzko, C. Hopwood, J. Kohn, D. Kruth, S. Hough, M. Dube, I. |
Citation: | Human Gene Therapy, 2002; 13(15):1809-1820 |
Publisher: | Mary Ann Liebert Inc Publ |
Issue Date: | 2002 |
ISSN: | 1043-0342 1557-7422 |
Statement of Responsibility: | Lisa Meertens, Yongjun Zhao, Suzana Rosic-Kablar, Liheng Li, Kin Chan, Howard Dobson, Cathy Gartley, Carolyn Lutzko, John Hopwood, Donald Kohn, Stephen Kruth, Margaret R. Hough, and Ian D. Dubé. Human Gene Therapy. |
Abstract: | Canine alpha-L-iduronidase (alpha-ID) deficiency is caused by a single base pair mutation in the alpha-ID gene, resulting in no enzyme activity in homozygous affected pups. The disease clinically resembles human mucopolysaccharidosis type I (MPSI). We used the canine MPSI model system to address the efficacy of a new retroviral vector, MND-MFG, containing the human alpha-ID cDNA (MND-MFG-alpha-ID) for direct in utero gene delivery to MPSI cells. In vitro, the MND-MFG-alpha-ID vector showed high-level, long-term expression of the transgene in both canine and human alpha-ID-deficient fibroblasts. The effectiveness of this vector for in utero gene transfer and expression in multiple tissues was assessed by injecting viral supernatants into MPSI fetuses and evaluating transduction efficiency and enzyme expression at various times after birth. Transduction of a spectrum of cell types and tissues was observed in all seven live-born pups and in one stillborn pup. Although enzyme activity was not detected in adult tissues from the seven surviving pups, significant alpha-ID enzyme activity was detected in both the liver and kidney of the deceased pup. Our combined gene delivery vector and in utero transfer approach, while encouraging in terms of overall gene transfer efficiency to multiple tissues and successful short-term gene expression, was unable to meet the important requirement of sustained in vivo gene expression. |
Keywords: | Liver Kidney Yolk Sac Cells, Cultured Jurkat Cells Fibroblasts Animals Animals, Newborn Dogs Humans Fetal Diseases Mucopolysaccharidosis I Disease Models, Animal Iduronidase DNA, Complementary Injections Injections, Intraperitoneal Transduction, Genetic Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic Tissue Distribution Pregnancy Genetic Vectors Female Genetic Therapy |
DOI: | 10.1089/104303402760372918 |
Published version: | http://dx.doi.org/10.1089/104303402760372918 |
Appears in Collections: | Aurora harvest Paediatrics publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.