Unknown

Dataset Information

0

Extended transgene expression from a nonintegrating adenoviral vector containing retroviral elements.


ABSTRACT: We studied the effects of specific retroviral elements in a first-generation serotype 5 adenoviral (Ad5) vector, AdLTR(2)EF1alpha-hEPO. This vector contains 858 base pair (bp) [251-bp envelope sequence plus 607-bp long-terminal repeat (LTR)] from Moloney murine leukemia virus (MoMLV), upstream of the human elongation factor-1alpha (EF1alpha) promoter and human erythropoietin (hEPO) cDNA, with the LTR sequence downstream of the polyadenylation signal. We compared expression of AdLTR(2)EF1alpha-hEPO with corresponding expressions of two conventional Ad5 vectors, AdEF1alpha-hEPO and AdCMV-hEPO, in vivo in submandibular glands in rats. Both the conventional vectors yielded low serum hEPO levels by day 7, and little change in hematocrits. In contrast, after receiving AdLTR(2)EF1alpha-hEPO, the rats showed elevated hEPO levels and hematocrits for 1-3 months. In vitro studies showed that the integration efficiencies of all the vectors were similar (approximately 10(-3)). Approximately 0.1% of the vector genomes were present 1 year after delivery in the case of each of the three vectors, primarily as intact linear double-strand DNA. The unique results seen with AdLTR(2)EF1alpha-hEPO are partly because of LTR enhancer activity. However, other cis-acting activity, which is not immunomodulatory but nevertheless influences promoter methylation, appears to be involved. A vector such as AdLTR(2)EF1alpha-hEPO may prove useful in clinical applications in which extended, but not "permanent," transgene expression is desirable.

SUBMITTER: Zheng C 

PROVIDER: S-EPMC5264529 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Extended transgene expression from a nonintegrating adenoviral vector containing retroviral elements.

Zheng Changyu C   Vitolo Joseph M JM   Zhang Weitian W   Mineshiba Fumi F   Chiorini John A JA   Baum Bruce J BJ  

Molecular therapy : the journal of the American Society of Gene Therapy 20080325 6


We studied the effects of specific retroviral elements in a first-generation serotype 5 adenoviral (Ad5) vector, AdLTR(2)EF1alpha-hEPO. This vector contains 858 base pair (bp) [251-bp envelope sequence plus 607-bp long-terminal repeat (LTR)] from Moloney murine leukemia virus (MoMLV), upstream of the human elongation factor-1alpha (EF1alpha) promoter and human erythropoietin (hEPO) cDNA, with the LTR sequence downstream of the polyadenylation signal. We compared expression of AdLTR(2)EF1alpha-hE  ...[more]

Similar Datasets

| S-EPMC3463356 | biostudies-literature
| S-EPMC20895 | biostudies-literature
| S-EPMC2587457 | biostudies-literature
| S-EPMC6455143 | biostudies-literature
| S-EPMC1629029 | biostudies-literature
| S-EPMC7352801 | biostudies-literature
| S-EPMC3666624 | biostudies-literature
| S-EPMC3757750 | biostudies-literature
| S-EPMC2835111 | biostudies-literature
| S-EPMC3640020 | biostudies-literature