Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of Nav1.7-targeting monoclonal antibodies.

Abstract	The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na+ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na+ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.
Authors	Sangsu Bang, Jiho Yoo, Xingrui Gong, Di Liu, Qingjian Han, Xin Luo, Wonseok Chang, Gang Chen, Sang-Taek Im, Yong Ho Kim, Judith A Strong, Ma-Zhong Zhang, Jun-Ming Zhang, Seok-Yong Lee, Ru-Rong Ji
Journal	Neuroscience bulletin (Neurosci Bull) Vol. 34 Issue 1 Pg. 22-41 (Feb 2018) ISSN: 1995-8218 [Electronic] Singapore
PMID	29333591 (Publication Type: Journal Article)
Chemical References	Antibodies, Monoclonal NAV1.5 Voltage-Gated Sodium Channel NAV1.7 Voltage-Gated Sodium Channel Recombinant Proteins SCN5A protein, human Scn9a protein, mouse Biotin
Topics	Animals Antibodies, Monoclonal (therapeutic use) Biotin (metabolism) Cells, Cultured Disease Models, Animal Female Ganglia, Spinal (cytology) HEK293 Cells Humans Hybridomas (chemistry) Hyperalgesia (drug therapy) Male Mice Mice, Inbred C57BL NAV1.5 Voltage-Gated Sodium Channel (metabolism) NAV1.7 Voltage-Gated Sodium Channel (chemistry, immunology, metabolism) Neuralgia (drug therapy, metabolism) Protein Binding (drug effects) Recombinant Proteins (biosynthesis, therapeutic use) Sensory Receptor Cells (drug effects, physiology)

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