High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: Prolongation of expression with immunosuppression

J.M. Howell; H. Lochmüller; A. O'Hara; S. Fletcher; B.A. Kakulas; B. Massie; J. Nalbantoglu; G. Karpati

doi:10.1089/hum.1998.9.5-629

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High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: Prolongation of expression with immunosuppression

Journal article

Peer reviewed

High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: Prolongation of expression with immunosuppression

J.M. Howell, H. Lochmüller, A. O'Hara, S. Fletcher, B.A. Kakulas, B. Massie, J. Nalbantoglu and G. Karpati

Human Gene Therapy, Vol.9(5), pp.629-634

1998

DOI: https://doi.org/10.1089/hum.1998.9.5-629

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Abstract

Replication-deficient adenovirus vectors (AdV) have been successfully used to transfer a truncated human dystrophin cDNA to skeletal muscle of dystrophin-deficient mdx mice. A dystrophin-deficient golden retriever dog model (GRMD) has been identified, which, unlike the mouse model, leads to a clinicopathological phenotype similar to that of Duchenne muscular dystrophy (DMD). We show for the first time that high-level dystrophin expression in skeletal muscle of GRMD dogs can be achieved by AdV-mediated gene transfer. However, a humoral and cellular immune response of the host against antigens of viral and transgene origin (similar to that occuring in mdx mice after AdV-mediated dystrophin gene transfer) leads to a decline of dystrophin expression over a 2-month period. Immunosuppression by cyclosporin significantly prolonged transgene expression. The GRMD model may help to solve the open questions pertaining to dystrophin gene transfer such as systemic delivery and improvement of muscle function before human trials for gene replacement therapy in DMD may be considered.

Details

Title: High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: Prolongation of expression with immunosuppression
Authors/Creators: J.M. Howell (Author/Creator) - Murdoch University
H. Lochmüller (Author/Creator)
A. O'Hara (Author/Creator)
S. Fletcher (Author/Creator) - Centre for Neuromuscular and Neurological Disorders
B.A. Kakulas (Author/Creator) - Centre for Neuromuscular and Neurological Disorders
B. Massie (Author/Creator)
J. Nalbantoglu (Author/Creator)
G. Karpati (Author/Creator)
Publication Details: Human Gene Therapy, Vol.9(5), pp.629-634
Publisher: Mary Ann Liebert Inc.
Identifiers: 991005541185007891
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.161 Virology - Identification & Sequencing; 1.161.479 Oncolytic Viruses
Web Of Science research areas: Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental
ESI research areas: Molecular Biology & Genetics