P2X3 (P2X purinoceptor 3) is predominantly expressed on nociceptive sensory neurons and plays a crucial role in signalling leading to chronic inflammatory pain and some features of neuropathic pain. Thus it represents a potential target for pain therapeutics. BoNT/A (botulinum neurooxin type A) effectively relieves certain types of pain through inhibiting the neuronal release of pain peptides. A recombinant single-chain variable fragment (scFv) antibody designated MH7C was generated against the extracellular domain of P2X3 using phage display. The genes encoding the scFv and activated di-chain form of BoNT/A without the C-terminal-binding subdomain (LC–HN–HCN/A) were ligated and expressed in Escherichia coli cells as a composite fusion protein. The purified protein bound and entered P2X3-containing sensory neurons, cleaved synaptosomal-associated protein of 25 kDa and inhibited the release of a pain peptide. This novel fusion protein designated ‘LC–HN–HCN/A–MH7C’ has potential clinical applications in the treatment of chronic inflammatory and sympathetically maintained neuropathic pain.
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September 2014
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Research Article|
August 07 2014
Targeted delivery of a SNARE protease to sensory neurons using a single chain antibody (scFv) against the extracellular domain of P2X3 inhibits the release of a pain mediator
Hui Ma;
Hui Ma
*School of Biotechnology, Dublin City University, Dublin 9, Ireland
†Targeted Therapeutics and Theranostics, Dublin City University, Dublin 9, Ireland
‡Biomedical Diagnostics Institute, Dublin City University, Dublin 9, Ireland
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Jianghui Meng;
Jianghui Meng
§International Centre for Neurotherapeutics, Dublin City University, Dublin 9, Ireland
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Jiafu Wang;
Jiafu Wang
§International Centre for Neurotherapeutics, Dublin City University, Dublin 9, Ireland
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Stephen Hearty;
Stephen Hearty
*School of Biotechnology, Dublin City University, Dublin 9, Ireland
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J. Oliver Dolly;
J. Oliver Dolly
†Targeted Therapeutics and Theranostics, Dublin City University, Dublin 9, Ireland
§International Centre for Neurotherapeutics, Dublin City University, Dublin 9, Ireland
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Richard O’Kennedy
Richard O’Kennedy
1
*School of Biotechnology, Dublin City University, Dublin 9, Ireland
†Targeted Therapeutics and Theranostics, Dublin City University, Dublin 9, Ireland
‡Biomedical Diagnostics Institute, Dublin City University, Dublin 9, Ireland
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
October 22 2013
Revision Received:
May 06 2014
Accepted:
May 20 2014
Accepted Manuscript online:
May 20 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 462 (2): 247–256.
Article history
Received:
October 22 2013
Revision Received:
May 06 2014
Accepted:
May 20 2014
Accepted Manuscript online:
May 20 2014
Citation
Hui Ma, Jianghui Meng, Jiafu Wang, Stephen Hearty, J. Oliver Dolly, Richard O’Kennedy; Targeted delivery of a SNARE protease to sensory neurons using a single chain antibody (scFv) against the extracellular domain of P2X3 inhibits the release of a pain mediator. Biochem J 1 September 2014; 462 (2): 247–256. doi: https://doi.org/10.1042/BJ20131387
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