Abstract
Bovine papillomavirus type 1 (BPV-1)-derived vectors may be useful for gene therapy because of their episomal maintenance at intermediate to high copy number and stable, high-level expression of gene products. To increase the safety of BPV-1 for human trials, the transforming early genes E5, E6, and E7 were deleted and a new vector, B45-Neo, was established and its transforming potential, episomal maintenance, and cDNA expression determined. Deletion of E5, E6, and E7, caused a decrease of the copy number to 80 in 3T3 fibroblasts when B45-Neo was compared to the parent vector that supported more than 1,000 copies per cell. No significant difference in the copy number, which ranged between 13 and 30 per cell, was detected in other cell lines of murine or human origin. The episomal maintenance of B45 and its ability to express cDNA was retained. B45-Neo, in contrast to BMG-Neo, however, was unable to transform NIH-3T3 and C1271 cells in soft agar colony assays. Unlike BMG-Neo, B45-Neo did not cause morphological changes in 3T3 and C1271 cells characteristic for transformation. It is concluded that B45-Neo is an efficient expression vector without detectable transforming activity and may be useful and safe for human gene therapy trials.
| Original language | English |
|---|---|
| Pages (from-to) | 325-333 |
| Number of pages | 9 |
| Journal | Human Gene Therapy |
| Volume | 6 |
| Issue number | 3 |
| State | Published - Jan 1 1995 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
Cite this
Construction of a novel bovine papillomavirus vector without detectable transforming activity suitable for gene transfer. / Ohe, Y.; Zhao, D.; Saijo, N.; Podack, E. R.
In: Human Gene Therapy, Vol. 6, No. 3, 01.01.1995, p. 325-333.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Construction of a novel bovine papillomavirus vector without detectable transforming activity suitable for gene transfer
AU - Ohe, Y.
AU - Zhao, D.
AU - Saijo, N.
AU - Podack, E. R.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - Bovine papillomavirus type 1 (BPV-1)-derived vectors may be useful for gene therapy because of their episomal maintenance at intermediate to high copy number and stable, high-level expression of gene products. To increase the safety of BPV-1 for human trials, the transforming early genes E5, E6, and E7 were deleted and a new vector, B45-Neo, was established and its transforming potential, episomal maintenance, and cDNA expression determined. Deletion of E5, E6, and E7, caused a decrease of the copy number to 80 in 3T3 fibroblasts when B45-Neo was compared to the parent vector that supported more than 1,000 copies per cell. No significant difference in the copy number, which ranged between 13 and 30 per cell, was detected in other cell lines of murine or human origin. The episomal maintenance of B45 and its ability to express cDNA was retained. B45-Neo, in contrast to BMG-Neo, however, was unable to transform NIH-3T3 and C1271 cells in soft agar colony assays. Unlike BMG-Neo, B45-Neo did not cause morphological changes in 3T3 and C1271 cells characteristic for transformation. It is concluded that B45-Neo is an efficient expression vector without detectable transforming activity and may be useful and safe for human gene therapy trials.
AB - Bovine papillomavirus type 1 (BPV-1)-derived vectors may be useful for gene therapy because of their episomal maintenance at intermediate to high copy number and stable, high-level expression of gene products. To increase the safety of BPV-1 for human trials, the transforming early genes E5, E6, and E7 were deleted and a new vector, B45-Neo, was established and its transforming potential, episomal maintenance, and cDNA expression determined. Deletion of E5, E6, and E7, caused a decrease of the copy number to 80 in 3T3 fibroblasts when B45-Neo was compared to the parent vector that supported more than 1,000 copies per cell. No significant difference in the copy number, which ranged between 13 and 30 per cell, was detected in other cell lines of murine or human origin. The episomal maintenance of B45 and its ability to express cDNA was retained. B45-Neo, in contrast to BMG-Neo, however, was unable to transform NIH-3T3 and C1271 cells in soft agar colony assays. Unlike BMG-Neo, B45-Neo did not cause morphological changes in 3T3 and C1271 cells characteristic for transformation. It is concluded that B45-Neo is an efficient expression vector without detectable transforming activity and may be useful and safe for human gene therapy trials.
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M3 - Article
C2 - 7779916
AN - SCOPUS:0028991823
VL - 6
SP - 325
EP - 333
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 3
ER -