REGULATED EXPRESSION OF ARTIFICIAL CHIMERIC GENES CONTAINED IN RETROVIRAL VECTORS - IMPLICATIONS FOR VIRUS-DIRECTED ENZYME PRODRUG THERAPY (VDEPT) AND OTHER GENE-THERAPY APPLICATIONS
Be. Huber et Ca. Richards, REGULATED EXPRESSION OF ARTIFICIAL CHIMERIC GENES CONTAINED IN RETROVIRAL VECTORS - IMPLICATIONS FOR VIRUS-DIRECTED ENZYME PRODRUG THERAPY (VDEPT) AND OTHER GENE-THERAPY APPLICATIONS, Journal of drug targeting., 3(5), 1996, pp. 349-356
Replication-defective retroviral vectors were created that contained c
himeric genes composed of either the albumin (ALB) or the alpha-fetopr
otein (AFP) transcriptional regulatory sequences linked to the coding
domain of the thymidine kinase gene from Varicella tester virus (VZV T
K). These viruses were used to infect the human hepatoblastoma cell li
ne, HepG2. Subsequent to infection, the infected cells were single-cel
l cloned. The level of expression of VZV TK from the chimeric genes co
rrelated with the level of endogenous expression of ALB or AFP in most
clones, indicating that the transcription of the chimeric VZV TK gene
is controlled in a similar manner to the endogenous ALB or AFP genes,
and that sites of viral integration are less important to overall gene
expression. Most importantly, as the expression of the endogenous ALB
gene was modified, so was expression of VZV TK from the ALB/VZV TK ch
imeric gene. This demonstrates that retroviruses can deliver a chimeri
c gene containing tissue-specific transcriptional regulatory sequences
that can respond to endogenous cell regulatory signals resulting in r
egulated gene expression.