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Site-Directed RNA Editing Technology As A Novel Analgesic

Published:
Lead Inventor: Joshua Rosenthal
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SUMMARY

Use of RNA editing to modify NaV1.7 sodium channels in nociceptors, making them permeable to Na+ and K+ ions reducing the excitability of these pain-signaling neurons, providing a reversible, selective, and potentially effective treatment for both acute and chronic pain

The Unmet Need: Methods to precisely and selectively alter NaV channels' function to manage pain without extensive side effects

  • Pain management, particularly for chronic and neuropathic pain, represents a significant challenge in medical treatment. Traditional pain therapies, including opioids, come with severe side effects such as addiction, tolerance, and overdose risks. Additionally, certain pain conditions like neuropathic pain and migraines remain inadequately managed with existing treatments. A promising strategy involves targeting nociceptors, which are sensory neurons responsible for pain perception. The voltage-gated sodium channels (NaV), especially NaV1.7, have been identified as critical in this regard because they are essential for the transmission of pain signals. However, effectively silencing these nociceptors without causing adverse effects such as cardiac and cognitive issues has been complex. The difficulty in targeting NaV1.7 specifically, while avoiding other sodium channels equally crucial for bodily functions, has been a significant barrier.

  • Current methodologies focusing on blocking voltage-gated sodium channels like NaV1.7 have not been entirely successful due to issues of selectivity and potential off-target effects that can lead to severe side effects. While some genetic mutations in NaV1.7 show a clear correlation to pain sensation, the pharmacological replication of these effects without unintended consequences has been challenging. Blocking the NaV channels can lead to broader systemic effects as these channels are present in various types of excitable cells, including heart and brain cells. Attempts to create more selective inhibitors have so far not adequately balanced efficacy with safety.

The Proposed Solution: Site-Directed RNA Editing to modify NaV1.7 sodium channels in nociceptors to replace opioids for pain treatment

  • The faculty inventor developed a RNA editing technique to modify NaV1.7 channels, which play a critical role in pain signaling, without causing side effects like cardiac or cognitive impairments. RNA editing changes the ion selectivity of NaV1.7 channels to allow both Na+ and K+ ions, effectively transforming these channels into electrical shunts that significantly reduce nociceptor excitability, thereby alleviating pain. This approach is highly selective, versatile, durable, reversible, and tunable with appropriate expression vectors, making it a promising solution for both acute and chronic pain scenarios.

ADVANTAGES

ADVANTAGES

  • Non-opioid pain treatment
  • Effective for neuropathic pain and migraines
  • Highly selective and reversible
  • Tunable
  • Utilizes natural epigenetic RNA editing
  • Avoids irreversible changes associated with DNA editing
  • Minimal cardiac and cognitive side effects
  • Potential extension to various neural disorders

APPLICATIONS

  • Neuropathic pain treatment
  • Migraine pain management
  • Chronic pain therapy
  • Acute pain relief