Encoded Therapeutics Inc. recently announced preclinical data demonstrating that its AAV9 microRNA (miRNA) gene therapy candidate achieved robust knockdown of SCN9A (Na_V1.7), a key mediator of pain signaling, in non-human primates (NHPs). The levels of target engagement in NHPs exceeded therapeutic thresholds observed in an established rodent pain model. Together, these findings support the potential of Encoded’s candidate as a one-time, non-opioid gene therapy for intractable chronic pain.

The candidate, developed through Encoded’s vector engineering platform, is designed to selectively and durably knock down SCN9A (Na_V1.7), a voltage-gated sodium channel that is well-established as a key mediator of pain sensitivity. Despite its validation, achieving both selective inhibition of Na_V1.7 and sufficient access to dorsal root ganglia (DRG) neurons remains a significant challenge. Encoded’s program leverages intrathecal delivery of clinically-validated AAV9 to enable selective knockdown of SCN9A in DRG sensory neurons, while limiting systemic biodistribution and potential off-target safety effects in organs such as the brain, heart, and liver.

“Chronic pain remains a highly prevalent and underserved neurological condition globally, with current treatments often offering limited relief, significant side effects, and a risk of dependency,” said Stephanie Tagliatela, Chief Scientific Officer of Encoded Therapeutics. “Our approach is uniquely designed to knock down a well-validated mediator of pain signaling, SCN9A (Na_V1.7), through intrathecal delivery of low-dose AAV9 to DRG neurons. By integrating validated biology, optimized delivery, and translational insights from our clinical-stage ETX101 program, we see the potential for our candidate to emerge as a one-time, non-opioid therapy capable of transforming care for people living with chronic pain.”

Preclinical Results

• NHP studies demonstrated 69% knockdown of SCN9A expression in lumbar DRG following a single dose of 1.5E13 vector genomes (vg)/animal, with minimal biodistribution in the brain, heart, and liver.
• In rats, consistent analgesic effects were observed in a well-established spared nerve injury model of chronic pain through 8 weeks post-dosing, with as little as 40% Scn9a knockdown sufficient to induce a durable analgesic response.
• Treatment was well-tolerated with no dose-limiting or treatment-related adverse findings across species.

These results establish a strong translational foundation for selective Na_V1.7 knockdown delivered with a validated AAV capsid, supporting potential broad application of gene therapy to a highly prevalent neurological disorder.

Intractable chronic pain is defined by persistent, severe discomfort that resists conventional treatments and profoundly disrupts quality of life. It affects millions of people worldwide, yet current therapies—including opioids—often provide limited relief and are associated with significant side effects and risk of dependency. Despite its widespread impact, there remains a lack of therapies that target the underlying mechanisms of chronic pain. This underscores an urgent need for innovative, safe, and effective approaches to address this persistent and debilitating condition.

Encoded Therapeutics is a clinical-stage genetic medicines company developing one-time therapies for severe neurological disorders. Our vector engineering platform enables highly selective, potent, and durable gene modulation. ETX101, our lead program, is designed to address the underlying cause of Dravet syndrome by selectively upregulating SCN1A and is currently in Phase 1/2 clinical trials. Building on this foundation, we are advancing additional programs to selectively modulate highly validated genetic targets in chronic pain, Angelman syndrome, and Alzheimer’s disease/tauopathies. With integrated discovery, development, and manufacturing capabilities, we are positioned to efficiently move programs from concept through the clinic. We are driven by a mission to pioneer transformative therapies that meaningfully improve the lives of patients and families affected by devastating neurological conditions. For more information, please visit www.encoded.com.