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Neonatal gene transfer using lentiviral vector for murine Pompe disease: long-term expression and glycogen reduction.
Gene Ther. 2010 Apr; 17(4):521-30.GT

Abstract

Pompe disease results from the deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to accumulated glycogen in the heart and the skeletal muscles, which causes cardiomyopathy and muscle weakness. In this study, we tested the feasibility of gene therapy for Pompe disease using a lentivirus vector (LV). Newborn GAA knockout mice were treated with intravenous injection of LV encoding human GAA (hGAA) through the facial superficial temporal vein. The transgene expression in the tissues was analyzed up to 24 weeks after treatment. Our results showed that the recombinant LV was efficient not only in increasing the GAA activity in tissues but also in decreasing their glycogen content. The examination of histological sections showed clearence of the glycogen storage in skeletal and cardiac muscles 16 and 24 weeks after a single vector injection. Levels of expressed hGAA could be detected in serum of treated animals until 24 weeks. No significant immune reaction to transgene was detected in most treated animals. Therefore, we show that LV-mediated delivery system was effective in correcting the biochemical abnormalities and that this gene transfer system might be suitable for further studies on delivering GAA to Pompe disease mouse models.

Authors+Show Affiliations

Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20033064

Citation

Kyosen, S O., et al. "Neonatal Gene Transfer Using Lentiviral Vector for Murine Pompe Disease: Long-term Expression and Glycogen Reduction." Gene Therapy, vol. 17, no. 4, 2010, pp. 521-30.
Kyosen SO, Iizuka S, Kobayashi H, et al. Neonatal gene transfer using lentiviral vector for murine Pompe disease: long-term expression and glycogen reduction. Gene Ther. 2010;17(4):521-30.
Kyosen, S. O., Iizuka, S., Kobayashi, H., Kimura, T., Fukuda, T., Shen, J., Shimada, Y., Ida, H., Eto, Y., & Ohashi, T. (2010). Neonatal gene transfer using lentiviral vector for murine Pompe disease: long-term expression and glycogen reduction. Gene Therapy, 17(4), 521-30. https://doi.org/10.1038/gt.2009.160
Kyosen SO, et al. Neonatal Gene Transfer Using Lentiviral Vector for Murine Pompe Disease: Long-term Expression and Glycogen Reduction. Gene Ther. 2010;17(4):521-30. PubMed PMID: 20033064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neonatal gene transfer using lentiviral vector for murine Pompe disease: long-term expression and glycogen reduction. AU - Kyosen,S O, AU - Iizuka,S, AU - Kobayashi,H, AU - Kimura,T, AU - Fukuda,T, AU - Shen,J, AU - Shimada,Y, AU - Ida,H, AU - Eto,Y, AU - Ohashi,T, Y1 - 2009/12/24/ PY - 2009/12/25/entrez PY - 2009/12/25/pubmed PY - 2010/8/19/medline SP - 521 EP - 30 JF - Gene therapy JO - Gene Ther. VL - 17 IS - 4 N2 - Pompe disease results from the deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to accumulated glycogen in the heart and the skeletal muscles, which causes cardiomyopathy and muscle weakness. In this study, we tested the feasibility of gene therapy for Pompe disease using a lentivirus vector (LV). Newborn GAA knockout mice were treated with intravenous injection of LV encoding human GAA (hGAA) through the facial superficial temporal vein. The transgene expression in the tissues was analyzed up to 24 weeks after treatment. Our results showed that the recombinant LV was efficient not only in increasing the GAA activity in tissues but also in decreasing their glycogen content. The examination of histological sections showed clearence of the glycogen storage in skeletal and cardiac muscles 16 and 24 weeks after a single vector injection. Levels of expressed hGAA could be detected in serum of treated animals until 24 weeks. No significant immune reaction to transgene was detected in most treated animals. Therefore, we show that LV-mediated delivery system was effective in correcting the biochemical abnormalities and that this gene transfer system might be suitable for further studies on delivering GAA to Pompe disease mouse models. SN - 1476-5462 UR - https://www.unboundmedicine.com/medline/citation/20033064/Neonatal_gene_transfer_using_lentiviral_vector_for_murine_Pompe_disease:_long_term_expression_and_glycogen_reduction_ L2 - http://dx.doi.org/10.1038/gt.2009.160 DB - PRIME DP - Unbound Medicine ER -