B6-hSCN9A Mice

Catalog Number: I001216

Strain Name: C57BL/6NCya-Scn9atm1(hSCN9A)/Cya

Genetic Background: C57BL/6NCya

One of Cyagen's HUGO-GT™ (Humanized Genomic Ortholog for Gene Therapy) Strains

 

Strain Description

The SCN9A gene encodes the Nav1.7 sodium channel protein, which is primarily expressed in the sensory and sympathetic nerves of the peripheral nervous system and is highly expressed in the dorsal root ganglia. Nav1.7 sodium channels play a crucial role in transmitting positively charged sodium ions within cells, essential for generating and transmitting electrical signals. When a person experiences pain, this protein releases sodium ion currents that amplify and stimulate nerve cells, sending electrical signals to the brain, thereby causing the sensation of pain. The SCN9A gene guides the entry of sodium ions into cells and facilitates communication between neurons. Mutations in the SCN9A gene can alter the function of sodium channels in the brain, disrupting neuronal communication and leading to various pain, olfactory, and neurological disorders such as erythromelalgia, paroxysmal extreme pain disorder, Dravet syndrome, small fiber neuropathy, and congenital insensitivity to pain. The abnormal protein function and symptoms resulting from gene mutations are directly related to the severity of the mutations, and different mutation types may lead to completely different conditions.

SCN9A is an excellent target for analgesic drug development. Downregulation of SCN9A expression can alleviate acute pain as well as certain types of inflammatory and neuropathic pain [1]. OliPass Corporation, a South Korean biotechnology company, has developed an antisense peptide nucleic acid (PNA) analgesic targeting SCN9A (OLP-1002), which has entered Phase 2a clinical trials. Antisense PNA is an artificially synthesized DNA/RNA mimic that inhibits RNA/DNA transcription and translation by complementary pairing with RNA/DNA sequences. The drug has shown strong analgesic effects and prolonged therapeutic duration in Australian patients with moderate to severe chronic osteoarthritis pain. It is estimated that due to its potent efficacy, excellent safety profile, and broad therapeutic scope, OLP-1002 could generate over $50 billion in market potential annually [2-4].

The B6-hSCN9A mouse is a mouse Scn9a humanized model, generated by replacing the mouse Scn9a gene (including the 5' UTR and 3' UTR) with the corresponding human SCN9A gene sequence using gene editing technology. This model can be used for studying the pathogenic mechanisms of neurological diseases such as erythromelalgia, Dravet syndrome, small fiber neuropathy, and congenital insensitivity to pain, as well as for screening analgesic drug candidates. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also provide customized services.

Strain Strategy


Figure 1. Gene editing strategy of B6-hSCN9A mice. The sequence from 5'UTR to ~884 bp downstream of 3'UTR of the mouse Scn9a was replaced with the sequence from 5'UTR to 3'UTR of the human SCN9A.

Application

  • Research on erythromelalgia, Dravet syndrome, small fiber neuropathy, and congenital insensitivity to pain;
  • Pathogenic mechanisms of other neurological diseases and analgesic drug research.

 

References

[1]Emery EC, Luiz AP, Wood JN. Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief. Expert Opin Ther Targets. 2016 Aug;20(8):975-83. doi: 10.1517/14728222.2016.1162295. Epub 2016 Apr 12. PMID: 26941184; PMCID: PMC4950419.
[2]Brazil R. Peptide Nucleic Acids Promise New Therapeutics and Gene Editing Tools. ACS Cent Sci. 2023 Jan 17;9(1):3-6.
[3]Biospace. (n.d.). Nav1.7 Selective Inhibitor OLP-1002 Shows Strong Efficacy and Long Therapeutic Duration According to Interim Findings from a Phase 2a Study in OA Patients. Retrieved from https://www.biospace.com/article/releases/nav1-7-selective-inhibitor-olp-1002-shows-strong-efficacy-and-long-therapeutic-duration-according-to-interim-findings-from-a-phase-2a-study-in-oa-patients/
[4]PR Newswire. (n.d.). Olipass Discloses Painful but Hilarious Clinical Findings from a Phase 2a Trial in OA Patients with Nav1.7 Selective Inhibitor OLP-1002. Retrieved from https://www.prnewswire.com/news-releases/olipass-discloses-painful-but-hilarious-clinical-findings-from-a-phase-2a-trial-in-oa-patients-with-nav1-7-selective-inhibitor-olp-1002--301985935.html