RRC ID 43247
Author Nakamura G, Maruyama H, Ishii S, Shimotori M, Kameda S, Kono T, Miyazaki J, Kulkarni AB, Gejyo F.
Title Naked plasmid DNA-based alpha-galactosidase A gene transfer partially reduces systemic accumulation of globotriaosylceramide in Fabry mice.
Journal Mol Biotechnol
Abstract Fabry disease is an X-linked recessive inborn metabolic disorder in which a deficiency in lysosomal enzyme alpha-galactosidase A (Gal A) causes the systemic accumulation of globotriaosylceramide (Gb3). Although many investigators have attempted to treat alpha-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 alpha-Gal A (pKSCX-alpha-Gal A) was rapidly injected into the left kidney of Fabry mice (pKSCX-alpha-Gal A mice). pKSCX was used for mock transfections (pKSCX mice). We confirmed that vector-derived human alpha-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-alpha-Gal A mice showed partial therapeutic effects: increased alpha-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.
Volume 38(2)
Pages 109-19
Published 2008-2-1
DOI 10.1007/s12033-007-9008-5
PMID 18219591
MeSH Animals Antibodies / immunology Body Weight COS Cells Chlorocebus aethiops DNA / genetics* Fabry Disease / enzymology* Fabry Disease / genetics Female Gene Expression Regulation, Enzymologic Humans Male Mice Organ Specificity Plasmids / genetics* RNA, Messenger / genetics Transgenes / genetics* Trihexosylceramides / metabolism* alpha-Galactosidase / genetics* alpha-Galactosidase / immunology alpha-Galactosidase / metabolism*
IF 2.022
Times Cited 13
Human and Animal Cells