Abstract
We have developed a novel vector system that uses a helper-dependent adenoviral vector as a carrier to deliver a fully functional retrovirus vector. The helper-dependent adenovirus (HDAd) can accommodate large inserts, provide high titers, and infect nondividing as well as dividing cells. However, adenoviral DNA is rarely integrated into the host cell genome, and its episomal expression is transient. Therefore we inserted a replication-competent, ecotropic retrovirus vector containing the green fluorescent protein (GFP) reporter gene as a second-stage component. The well-characterized host species tropism of each vector component provided a stringent biological assay system that demonstrates the two-stage transduction mechanism of the hybrid vector, because the adenovirus stage can efficiently transduce human cells but cannot replicate in murine cells, and conversely, the ecotropic retrovirus stage cannot enter human cells but can efficiently proliferate in murine cells, resulting in permanent integration and progressive spread of reporter gene expression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 599-608 |
| Number of pages | 10 |
| Journal | Molecular Therapy |
| Volume | 5 |
| Issue number | 5 I |
| DOIs | |
| State | Published - 2002 |
| Externally published | Yes |
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Keywords
- Adenovirus
- Gene therapy
- Helper-dependent adenovirus
- Hybrid vector
- Replication-competent retrovirus
- Retrovirus
ASJC Scopus subject areas
- Molecular Biology
Cite this
A novel, helper-dependent, adenovirus-retrovirus hybrid vector : Stable transduction by a two-stage mechanism. / Soifer, Harris; Higo, Collin; Logg, Christopher R.; Jih, L. J L; Shichinohe, Toshiaki; Harboe-Schmidt, Erik; Mitani, Kohnosuke; Kasahara, Noriyuki.
In: Molecular Therapy, Vol. 5, No. 5 I, 2002, p. 599-608.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel, helper-dependent, adenovirus-retrovirus hybrid vector
T2 - Stable transduction by a two-stage mechanism
AU - Soifer, Harris
AU - Higo, Collin
AU - Logg, Christopher R.
AU - Jih, L. J L
AU - Shichinohe, Toshiaki
AU - Harboe-Schmidt, Erik
AU - Mitani, Kohnosuke
AU - Kasahara, Noriyuki
PY - 2002
Y1 - 2002
N2 - We have developed a novel vector system that uses a helper-dependent adenoviral vector as a carrier to deliver a fully functional retrovirus vector. The helper-dependent adenovirus (HDAd) can accommodate large inserts, provide high titers, and infect nondividing as well as dividing cells. However, adenoviral DNA is rarely integrated into the host cell genome, and its episomal expression is transient. Therefore we inserted a replication-competent, ecotropic retrovirus vector containing the green fluorescent protein (GFP) reporter gene as a second-stage component. The well-characterized host species tropism of each vector component provided a stringent biological assay system that demonstrates the two-stage transduction mechanism of the hybrid vector, because the adenovirus stage can efficiently transduce human cells but cannot replicate in murine cells, and conversely, the ecotropic retrovirus stage cannot enter human cells but can efficiently proliferate in murine cells, resulting in permanent integration and progressive spread of reporter gene expression.
AB - We have developed a novel vector system that uses a helper-dependent adenoviral vector as a carrier to deliver a fully functional retrovirus vector. The helper-dependent adenovirus (HDAd) can accommodate large inserts, provide high titers, and infect nondividing as well as dividing cells. However, adenoviral DNA is rarely integrated into the host cell genome, and its episomal expression is transient. Therefore we inserted a replication-competent, ecotropic retrovirus vector containing the green fluorescent protein (GFP) reporter gene as a second-stage component. The well-characterized host species tropism of each vector component provided a stringent biological assay system that demonstrates the two-stage transduction mechanism of the hybrid vector, because the adenovirus stage can efficiently transduce human cells but cannot replicate in murine cells, and conversely, the ecotropic retrovirus stage cannot enter human cells but can efficiently proliferate in murine cells, resulting in permanent integration and progressive spread of reporter gene expression.
KW - Adenovirus
KW - Gene therapy
KW - Helper-dependent adenovirus
KW - Hybrid vector
KW - Replication-competent retrovirus
KW - Retrovirus
UR - http://www.scopus.com/inward/record.url?scp=0036104279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036104279&partnerID=8YFLogxK
U2 - 10.1006/mthe.2002.0586
DO - 10.1006/mthe.2002.0586
M3 - Article
C2 - 11991751
AN - SCOPUS:0036104279
VL - 5
SP - 599
EP - 608
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 5 I
ER -