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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.

Publication ,  Journal Article
Bang, S; Yoo, J; Gong, X; Liu, D; Han, Q; Luo, X; Chang, W; Chen, G; Im, S-T; Kim, YH; Strong, JA; Zhang, M-Z; Zhang, J-M; Lee, S-Y; Ji, R-R
Published in: Neurosci Bull
February 2018

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.

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Published In

Neurosci Bull

DOI

EISSN

1995-8218

Publication Date

February 2018

Volume

34

Issue

1

Start / End Page

22 / 41

Location

Singapore

Related Subject Headings

  • Sensory Receptor Cells
  • Recombinant Proteins
  • Protein Binding
  • Neurology & Neurosurgery
  • Neuralgia
  • NAV1.7 Voltage-Gated Sodium Channel
  • NAV1.5 Voltage-Gated Sodium Channel
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

APA
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Bang, S., Yoo, J., Gong, X., Liu, D., Han, Q., Luo, X., … Ji, R.-R. (2018). 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. Neurosci Bull, 34(1), 22–41. https://doi.org/10.1007/s12264-018-0203-0
Bang, Sangsu, Jiho Yoo, Xingrui Gong, Di Liu, Qingjian Han, Xin Luo, Wonseok Chang, et al. “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.Neurosci Bull 34, no. 1 (February 2018): 22–41. https://doi.org/10.1007/s12264-018-0203-0.
Bang S, Yoo J, Gong X, Liu D, Han Q, Luo X, Chang W, Chen G, Im S-T, Kim YH, Strong JA, Zhang M-Z, Zhang J-M, Lee S-Y, Ji R-R. 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. Neurosci Bull. 2018 Feb;34(1):22–41.
Journal cover image

Published In

Neurosci Bull

DOI

EISSN

1995-8218

Publication Date

February 2018

Volume

34

Issue

1

Start / End Page

22 / 41

Location

Singapore

Related Subject Headings

  • Sensory Receptor Cells
  • Recombinant Proteins
  • Protein Binding
  • Neurology & Neurosurgery
  • Neuralgia
  • NAV1.7 Voltage-Gated Sodium Channel
  • NAV1.5 Voltage-Gated Sodium Channel
  • Mice, Inbred C57BL
  • Mice
  • Male