Journal
MOLECULAR THERAPY
Volume 4, Issue 1, Pages 36-44Publisher
ACADEMIC PRESS INC
DOI: 10.1006/mthe.2000.0410
Keywords
adenovirus; retrovirus; chimeric; hematopoietic; Mo7e
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Funding
- NHLBI NIH HHS [P01 HL53750] Funding Source: Medline
- NIDDK NIH HHS [P30 DK 47754, R21 DK55590] Funding Source: Medline
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Inefficient gene transfer has limited the success of gene therapy in the hematopoietic system. Here we develop a novel chimeric adenovirus (Ad) vector containing Ad serotype 11 fiber-modified capsids and E1/E3 deleted viral genomes (Ad5/11) or genomes devoid of all viral genes (Delta Ad5/11). The capsid-modified vectors transduced human hematopoietic cells more efficiently than the unmodified Ad5-based vector. The absence of viral genes from the Delta Ad5/11 vector allowed for transduction without the associated toxicity seen with the first-generation E1/E3 deleted vector. Chimeric vectors were used for transient expression of the ecotropic retrovirus receptor (ecoR) in Mo7e cells (a CD34-positive, c-Kit-positive, growth-factor-dependent human cell line) as a model for human hematopoietic progenitor cells. Expression of ecoR conferred susceptibility to subsequent retroviral transduction. The Delta Ad5/11 vector used to express ecoR allowed for expansion of retrovirally transduced cells, whereas transduction with the first-generation Ad5/11 vector resulted in cytotoxicity and, over time, loss of cells expressing the retrovirus-vector-derived transgene.
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