Imperial College London
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DrVikashReebye

Faculty of Medicine, Department of Surgery & Cancer

Research Fellow in Gene Activation
 
 
 
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Contact

 

+44 (0)20 3313 2047v.reebye

 
 
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Location

 

B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Yoon:2019:10.1016/j.omtn.2019.08.017,
author = {Yoon, S and Huang, K-W and Andrikakou, P and Vasconcelos, D and Swiderski, P and Reebye, V and Sodergren, M and Habib, N and Rossi, JJ},
doi = {10.1016/j.omtn.2019.08.017},
journal = {Molecular Therapy : Nucleic Acids},
pages = {142--154},
title = {Targeted delivery of C/EBP alpha-saRNA by RNA aptamers shows anti-tumor effects in a mouse model of advanced PDAC},
url = {http://dx.doi.org/10.1016/j.omtn.2019.08.017},
volume = {18},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies; it preferentially metastasizes to the liver and is the main cause of death from this disease. In previous studies, small activating RNA against CCAAT/enhancer-binding protein-α (C/EBPα-saRNA) demonstrated efficacy of PDAC in a local subcutaneous tumor model. In this study, we focused on the efficacy of C/EBPα-saRNA in advanced stage PDAC. For targeted delivery, we selected a new anti-transferrin receptor aptamer (TR14), which demonstrated a high binding affinity to target proteins. The TR14 aptamer was internalized with clathrin-mediated endocytosis, distributed in early endosome, late endosome, and lysosome subcellularly. To investigate its anti-tumor effects to advanced PDAC, we conjugated C/EBPα-saRNA to TR14. Treatment of pancreatic cancer cells with the conjugates upregulated expression of C/EBPα and its downstream target p21, and inhibited cell proliferation. For in vivo assays, we established an advanced PDAC mouse model by engrafting luciferase reporter-PANC-1 cells directly into the livers of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After treatment of aptamer-C/EBPα conjugates, we observed significant reduction of tumor growth in this advanced PDAC mouse model. Combinational treatment of the conjugates with gemcitabine also demonstrated enhanced anti-tumor effects in advanced PDAC. This suggests that aptamer-C/EBPα conjugates could be used as an adjuvant, along with other conventional anti-cancer drugs in advanced PDAC. In conclusion, targeted delivery of C/EBPα-saRNAs by aptamers might have potential therapeutic effects in advanced PDAC.
AU  - Yoon,S
AU  - Huang,K-W
AU  - Andrikakou,P
AU  - Vasconcelos,D
AU  - Swiderski,P
AU  - Reebye,V
AU  - Sodergren,M
AU  - Habib,N
AU  - Rossi,JJ
DO  - 10.1016/j.omtn.2019.08.017
EP  - 154
PY  - 2019///
SN  - 2162-2531
SP  - 142
TI  - Targeted delivery of C/EBP alpha-saRNA by RNA aptamers shows anti-tumor effects in a mouse model of advanced PDAC
T2  - Molecular Therapy : Nucleic Acids
UR  - http://dx.doi.org/10.1016/j.omtn.2019.08.017
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000500716400014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.sciencedirect.com/science/article/pii/S2162253119302306?via%3Dihub
UR  - http://hdl.handle.net/10044/1/78983
VL  - 18
ER  -
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