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Title 

Efficient targeting and tumor retardation effect of pancreatic adenocarcinoma up-regulated factor (PAUF)-specific RNA replacement in pancreatic cancer mouse model

Authors 

Y H KimJ Y MoonE O KimS J LeeS H KangS K KimK HeoYangsoon LeeSang Seok KohI H Kim

Publisher 

Elsevier

Issue Date 

2014

Citation 

Cancer Letters, vol. 344, no. 2, pp. 223-231

Keywords 

Gene therapyPancreatic cancerPAUFRNA replacement

Abstract 

The soluble protein pancreatic adenocarcinoma up-regulated factor (PAUF) plays an important role in pancreatic tumor progression and has begun to attract attention as a therapeutic target for pancreatic cancer. We herein present PAUF RNA-targeting gene therapy strategies with both targeting and therapeutic function using trans-splicing ribozyme (TSR) in pancreatic cancer. We developed adenoviral PAUF-targeting TSR (Rz) containing a PAUF-specific internal guide sequence (IGS) determined by library screening. This Rz harbors suicide gene, herpes simplex virus thymidine kinase (HSV-tk) or firefly luciferase (Luc) as a transgene for 3' exon replacement of PAUF RNAs. Ad-Rz-TK, Rz harboring the HSV-tk, showed significant inhibition of tumor growth in vivo as well as PAUF-dependent cell death in vitro via a successful trans-splicing reaction. Selective induction of Rz-controlled transgene in PAUF-expressing pancreatic cancer was confirmed through noninvasive in vivo imaging; a luminescence signal from Rz harboring Luc (Ad-Rz-Luc) was detectable only in pancreatic tumor sites, not in normal mice. In addition, a [125I] FIAU signal reflecting thymidine kinase expression through SPECT and ex vivo biodistribution was co-localized with the tumor sites when we treated with Ad-Rz-TK in orthotopic xenograft model. Taken together, these results imply that PAUF-targeting TSR can contribute to successful targeted gene therapy for pancreatic cancer.

ISSN 

0304-3835

Link 

http://dx.doi.org/10.1016/j.canlet.2013.10.028

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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