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Molecular Biotechnology

, Volume 38, Issue 2, pp 109–119 | Cite as

Naked Plasmid DNA-Based α-Galactosidase A Gene Transfer Partially Reduces Systemic Accumulation of Globotriaosylceramide in Fabry Mice

  • Gen Nakamura
  • Hiroki Maruyama
  • Satoshi Ishii
  • Masaaki Shimotori
  • Shigemi Kameda
  • Toru Kono
  • Jun-ichi Miyazaki
  • Ashok B. Kulkarni
  • Fumitake Gejyo
Research

Abstract

Fabry disease is an X-linked recessive inborn metabolic disorder in which a deficiency in lysosomal enzyme α-galactosidase A (Gal A) causes the systemic accumulation of globotriaosylceramide (Gb3). Although many investigators have attempted to treat α-Gal A knock-out mice (Fabry mice) with gene therapy, no report has demonstrated therapeutic effects by the retrograde renal vein injection of naked DNA. We recently developed a naked plasmid vector-mediated kidney-targeted gene transfer technique. A solution containing naked plasmid DNA encoding human α-Gal A (pKSCX-α-Gal A) was rapidly injected into the left kidney of Fabry mice (pKSCX-α-Gal A mice). pKSCX was used for mock transfections (pKSCX mice). We confirmed that vector-derived human α-Gal A mRNA was present in the left kidney but not in other tissues, by reverse transcriptase polymerase chain reaction. Compared with the pKSCX mice, the pKSCX-α-Gal A mice showed partial therapeutic effects: increased α-Gal A activity in the injected kidney and in the liver, heart, and plasma, and decreased Gb3 in the injected kidney, contralateral kidney, liver, heart, and spleen. Our results demonstrated that, although further studies are needed to improve the outcome, this method has promise as a potential treatment option for Fabry disease.

Keywords

Naked plasmid DNA Fabry disease Catheter-based gene transfer Renal vein injection CAG promoter Hydrodynamics-based transfection 

Notes

Acknowledgments

This work was partly supported by a Grant-in-aid for Scientific Research (C) from the Ministry of Education, Science, Sports, and Culture and a Yujin Memorial Grant to Hiroki Maruyama.

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Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Gen Nakamura
    • 1
  • Hiroki Maruyama
    • 2
  • Satoshi Ishii
    • 3
  • Masaaki Shimotori
    • 1
  • Shigemi Kameda
    • 1
  • Toru Kono
    • 4
  • Jun-ichi Miyazaki
    • 5
  • Ashok B. Kulkarni
    • 6
  • Fumitake Gejyo
    • 1
  1. 1.Division of Clinical Nephrology and RheumatologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  2. 2.Department of Clinical NephroscienceNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  3. 3.Department of Agricultural and Life SciencesObihiro University of Agriculture and Veterinary MedicineObihiroJapan
  4. 4.Division of Gastroenterology, Department of Surgery IIAsahikawa Medical CollegeAsahikawaJapan
  5. 5.Division of Stem Cell Regulation Research, G6Osaka University Medical SchoolSuitaJapan
  6. 6.Functional Genomics Section CDBRB NIDCR, NIHBethesdaUSA

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