Imperial College London
Alternate

DrNeloferSyed

Faculty of Medicine, Department of Brain Sciences

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 5292n.syed

 
 
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Location

 

E506Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Przystal:2013:10.1016/j.molonc.2012.08.001,
author = {Przystal, JM and Umukoro, E and Stoneham, CA and Yata, T and O'Neill, K and Syed, N and Hajitou, A},
doi = {10.1016/j.molonc.2012.08.001},
journal = {Molecular Oncology},
pages = {55--66},
title = {Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno-associated virus/phage},
url = {http://dx.doi.org/10.1016/j.molonc.2012.08.001},
volume = {7},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements of adenoassociated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets by displaying an integrin tumortargeting ligand on the phage capsid. However, inherent limitations in bacteriophage mean that these AAVP vectors still need to be improved. One of the limitations of AAVP in mammalian cells may be its susceptibility to proteasomal degradation. The proteasome is upregulated in cancer and it is known that it constitutes a barrier to gene delivery by certain eukaryotic viruses. We report here that inhibition of proteasome improved targeted reporter gene delivery by AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector administration to tumorbearing mice. We also show enhanced targeted tumor cell killing by AAVP upon proteasome inhibition. The AAVP particles persisted significantly in cancer cells in vitro and in tumors in vivo after systemic administration, and accumulated polyubiquitinated coat proteins. Our results suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and indicate that a combination of proteasomeinhibiting drugs and AAVP should be considered for clinical anticancer therapy.
AU  - Przystal,JM
AU  - Umukoro,E
AU  - Stoneham,CA
AU  - Yata,T
AU  - O'Neill,K
AU  - Syed,N
AU  - Hajitou,A
DO  - 10.1016/j.molonc.2012.08.001
EP  - 66
PY  - 2013///
SN  - 1574-7891
SP  - 55
TI  - Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno-associated virus/phage
T2  - Molecular Oncology
UR  - http://dx.doi.org/10.1016/j.molonc.2012.08.001
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000314381800005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://febs.onlinelibrary.wiley.com/doi/full/10.1016/j.molonc.2012.08.001
UR  - http://hdl.handle.net/10044/1/82271
VL  - 7
ER  -
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