Monoclonal antibodies for precision delivery of analgesic therapeutics to peripheral nervous system neurons

Peripheral neuropathy affects 15–20 million Americans, with chronic pain as a major and debilitating manifestation, driving over $10 billion in annual healthcare costs. Existing therapies offer limited efficacy and are constrained by systemic side effects and risks of misuse or addiction. This underscores a critical unmet need for nociceptive circuit–targeted precision neurotherapies.

This proposal introduces a first-in-class platform that harnesses a nociceptor-enriched target protein as a selective delivery address. By developing monoclonal antibodies and, subsequently, antibody–drug (ADC) and antibody–oligonucleotide conjugates (AOC) targeting this nociceptor protein, this strategy enables targeted delivery of potent payloads directly to pain-sensing neurons. This approach aims to achieve durable modulation of nociceptor function while minimizing systemic exposure.

The primary objectives are: (1) to generate and validate high-affinity, extracellular-binding, target protein–specific antibodies suitable for conjugation, and (2) to characterize their internalization properties to guide optimal payload/modality selection.

Successful completion will establish a scalable, patentable platform with broad applicability across chronic pain indications, enabling access to previously undruggable intracellular targets and positioning this technology for meaningful clinical and commercial impact.