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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
Statement of
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
Yolk Sac
Cells, Cultured
Jurkat Cells
Animals, Newborn
Fetal Diseases
Mucopolysaccharidosis I
Disease Models, Animal
DNA, Complementary
Injections, Intraperitoneal
Transduction, Genetic
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Tissue Distribution
Genetic Vectors
Genetic Therapy
DOI: 10.1089/104303402760372918
Appears in Collections:Aurora harvest
Paediatrics publications

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