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Recombinant adeno-associated virus mediated gene transfer in a mouse model for homocystinuria

Authors
 Eun-Sook Park  ;  Hyun-Jeong Oh  ;  Warren D Kruger  ;  Sung-Chul Jung  ;  Jin-Sung Lee 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.38(6) : 652-661, 2006-12 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2006-12
MeSH
Animals ; Cell Line ; Cystathionine beta-Synthase / genetics ; Cystathionine beta-Synthase / metabolism ; DNA, Recombinant / genetics ; Dependovirus / genetics* ; Disease Models, Animal ; Gene Transfer Techniques ; Genetic Therapy ; Homocysteine / blood ; Homocystinuria / enzymology ; Homocystinuria / genetics* ; Homocystinuria / pathology ; Homocystinuria / therapy ; Humans ; Immunohistochemistry ; Mice ; Survival Rate
Abstract
Homocystinuria is a metabolic disorder caused by a deficiency of cystathionine beta-synthase (CBS). The major clinical symptoms of this disease are mental retardation, lens dislocation, vascular disease with life-threatening thromboembolisms, and skeletal deformities. The major treatments for CBS deficiency include pharmacologic doses of pyridoxine or dietary restriction of methionine. There is currently no effective long-term treatment to lower the elevated plasma levels of homocysteine. However, gene therapy could be an effective novel approach for the treatment of homocystinuria. A recombinant adeno- associated virus vector carrying human CBS cDNA (rAAV-hCBS) was constructed and administered to CBS-/- mice by intramuscular (IM) and intraperitoneal (IP) injections. Serum homocysteine concentrations significantly decreased in treated mice compared with age-matched controls two weeks after treatment. The treated CBS-/- mice had life spans 3-7 days longer compared with untreated CBS-/- mice. In CBS-/- mice treated with rAAV-hCBS via IP injection, the vector was detected in all organs examined including liver, spleen, and kidney, and CBS gene expression was observed by immunohistochemical staining in the liver. These results indicate the efficacy of gene delivery and demonstrate the possibility of gene therapy mediated by AAV gene transfer in this mouse model of homocystinuria.
Files in This Item:
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DOI
10.1038/emm.2006.77
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jin-Sung(이진성) ORCID logo https://orcid.org/0000-0002-1262-8597
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/178903
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