Journal
HUMAN GENE THERAPY
Volume 24, Issue 8, Pages 766-775Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2012.132
Keywords
-
Categories
Funding
- Swedish Cancer Society [10-0105, 10-0552]
- Swedish Children Cancer Foundation [PROJ10/027, NBCNSPDHEL10/013, PROJ11/062]
- Gunnar Nilsson's Cancer Foundation
- Swedish Research Council [K2013-55X-22191-01-3]
- Marcus and Marianne Wallenberg's Foundation
Ask authors/readers for more resources
Secretogranin III (SGC3) belongs to the granin family and is highly expressed in endocrine and neural tissues. The human SCG3 promoter has not yet been characterized. We identified that a 0.5-kb DNA fragment upstream of the SCG3 gene can selectively drive transgene expression in neuroblastoma cell lines. The strength of transgene expression was further increased, with specificity maintained, by addition of the human achaete-scute complex homolog 1 (ASH1) enhancer. We developed an oncolytic serotype 5-based adenovirus, in which the SCG3 promoter and ASH1 enhancer drive E1A gene expression. The virus was further modified with a cell-penetrating peptide (Tat-PTD) in the viral capsid, which we have previously shown results in increased adenovirus transduction efficiency of many neuroblastoma cell lines. The virus, Ad5PTD(ASH1-SCG3-E1A), shows selective and efficient killing of neuroblastoma cell lines in vitro, including cisplatin-, etoposide-, and doxorubicin-insensitive neuroblastoma cells. Furthermore, it delays tumor growth and thereby prolonged survival for nude mice harboring subcutaneous human neuroblastoma xenograft. In conclusion, we report a novel oncolytic adenovirus with potential use for neuroblastoma therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available