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    Vector sequences are not detected in tumor tissue from research subjects with ornithine transcarbamylase deficiency who previously received adenovirus gene transfer

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    Authors
    Zhong, Li
    Li, Shaoyong
    Li, Mengxin
    Xie, Jun
    Zhang, Yu
    Lee, Brendan
    Batshaw, Mark L.
    Wilson, James M.
    Gao, Guangping
    UMass Chan Affiliations
    Department of Microbiology and Physiology Systems
    Division of Hematology/Oncology, Department of Pediatrics
    Gene Therapy Center
    Document Type
    Journal Article
    Publication Date
    2013-09-01
    Keywords
    Aged
    Carcinoma, Hepatocellular
    Colorectal Neoplasms
    Dependovirus
    Female
    Gene Transfer Techniques
    Genetic Therapy
    Humans
    Liver Neoplasms
    Middle Aged
    Ornithine Carbamoyltransferase
    Ornithine Carbamoyltransferase Deficiency Disease
    Research Subjects
    Congenital, Hereditary, and Neonatal Diseases and Abnormalities
    Genetic Processes
    Genetics
    Molecular Genetics
    Neoplasms
    Nervous System Diseases
    Therapeutics
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3768231/
    Abstract
    A 66-year-old woman heterozygous for a mutation in the ornithine transcarbamylase gene (Otc) participated in a phase I gene therapy trial for OTC deficiency. She received an adenovirus (Ad) vector expressing the functional OTC gene by intraportal perfusion. Fourteen years later she developed and subsequently died of hepatocellular carcinoma. A second subject, a 45-year-old woman, enrolled in the same trial presented with colon cancer 15 years later. We sought to investigate a possible association between the development of a tumor and prior adenoviral gene transfer in these two subjects. We developed and validated a sensitive nested polymerase chain reaction assay for recovering recombinant Ad sequences from host tissues. Using this method, we could not detect any Ad vector DNA in either tumor or normal tissue from the two patients. Our results are informative in ruling out the possibility that the adenoviral vector might have contributed to the development of cancer in those two subjects.
    Source
    Hum Gene Ther. 2013 Sep;24(9):814-9. doi: 10.1089/hum.2013.118. Link to article on publisher's website
    DOI
    10.1089/hum.2013.118
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/30291
    PubMed ID
    24010702
    Related Resources
    Link to article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1089/hum.2013.118
    Scopus Count
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