Abstract:
:Glycogen storage disease type II (GSD-II) is a lethal, autosomal recessive metabolic myopathy caused by a lack of acid-alpha-glucosidase (GAA) activity in the cardiac and skeletal muscles. Absence of adequate intralysosomal GAA activity results in massive amounts of glycogen accumulation in multiple muscle groups, resulting in morbidity and mortality secondary to respiratory embarrassment and/or cardiomyopathy. In a mouse model of GSD-II, we demonstrate that infection of the murine liver with a modified adenovirus (Ad) vector encoding human GAA (hGAA) resulted in long-term persistence of the vector in liver tissues for at least 6 months. Despite both a rapid shutdown of hGAA mRNA expression from the vector, as well as the elicitation of anti-hGAA antibody responses (hGAA is a foreign antigen in this model), the hGAA secreted by the liver was taken up by all muscle groups analyzed and, remarkably, persisted in them for at least 6 months. The persistence of the protein also correlated with long-term correction of pathologic intramuscular glycogen accumulations in all muscle groups tested, but most notably the cardiac tissues, which demonstrated a significantly decreased glycogen content for at least 190 days after a single vector injection. The results suggest that gene therapy strategies may have the potential to significantly improve the clinical course for GSD-II patients.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Ding EY,Hodges BL,Hu H,McVie-Wylie AJ,Serra D,Migone FK,Pressley D,Chen YT,Amalfitano Adoi
10.1089/104303401750195917keywords:
subject
Has Abstractpub_date
2001-05-20 00:00:00pages
955-65issue
8eissn
1043-0342issn
1557-7422journal_volume
12pub_type
杂志文章abstract::Adeno-associated viral (AAV) vectors are becoming increasingly popular in basic research as well as in clinical gene therapy. Due to its exceptional resistance against physical and chemical stress, however, the increasing use of AAV in laboratories and clinics around the globe raises safety concerns. Proper decontamin...
journal_title:Human gene therapy
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journal_title:Human gene therapy
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Human gene therapy
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.5-621
更新日期:1998-03-20 00:00:00
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journal_title:Human gene therapy
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doi:10.1089/hum.1997.8.14-1675
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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pub_type: 杂志文章
doi:10.1089/hum.2015.130
更新日期:2016-01-01 00:00:00
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更新日期:2016-05-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.241
更新日期:2021-01-15 00:00:00
abstract::Immunotherapy with whole cell cancer vaccines has been tested in various tumor types. This study investigated the safety profile and antitumor activity of an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant human interleukin-2 and human interferon-gamma. Thirty HLA-A*0201-matched patients with pr...
journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:2009-12-01 00:00:00
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pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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pub_type: 杂志文章,多中心研究
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更新日期:2006-02-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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