Type

Journal Article

Authors

Richard O'Kennedy
J Oliver Dolly
Stephen Hearty
Jiafu Wang
Jianghui Meng
Hui Ma

Subjects

Biochemistry

Topics
sensory receptor cells incobotulinumtoxina metabolism rats humans recombinant fusion proteins pharmacology cytology drug effects immunology synaptosomal associated protein 25 rabbits female pain chemistry botulinum toxins type a genetics animals single chain antibodies cells cultured mice ganglia spinal calcitonin gene related peptide receptors purinergic p2x3

Targeted delivery of a SNARE protease to sensory neurons using a single chain antibody (scFv) against the extracellular domain of P2X(3) inhibits the release of a pain mediator. (2014)

Abstract 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.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Richard O'Kennedy, J Oliver Dolly, Stephen Hearty, Jiafu Wang, Jianghui Meng, Hui Ma

Experts in our system

1
R O'Kennedy
Dublin City University
Total Publications: 197
 
2
J Oliver Dolly
Dublin City University
Total Publications: 34
 
3
Stephen Hearty
Dublin City University
Total Publications: 27
 
4
Jiafu Wang
Dublin City University
Total Publications: 27
 
5
Jianghui Meng
Dublin City University
Total Publications: 19
 
6
Hui Ma
Dublin City University
Total Publications: 8