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bioRxiv · 10.1101/2025.11.13.688281

Development of Recombinant Anti-TLR2 Antibodies and PLGA Nanoparticle-based Gene Therapy for the Treatment of Neuropathic Pain

Lee, S.·Jeon, J.·Lee, H.·Barcelona, E. E.·Hong, J.·Lee, S. J.
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Abstract

Neuroinflammation is a key contributor to neuropathic pain, with microglial Toll-like receptor 2 (TLR2) playing a central role in initiating and sustaining proinflammatory responses. However, existing TLR2-targeting antibody therapies are limited by poor delivery to the central nervous system and short-lived efficacy. We developed a non-viral gene therapy strategy using biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to deliver recombinant anti-TLR2 antibody genes. High-affinity nanobody and single-chain variable fragment candidates were selected through phage display screening and shown to suppress TLR2-dependent signaling both in vitro and in vivo. In mouse models of neuropathic pain, a single intrathecal administration of PLGA NP-encapsulated antibody genes produced robust and sustained analgesia, accompanied by reduced glial activation and proinflammatory cytokine expression. These findings demonstrate a modular NP-based platform for sustained antibody expression in the central nervous system and establish its potential for the treatment of chronic pain driven by innate immune activation.

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Lee, S., Jeon, J., Lee, H., Barcelona, E. E., Hong, J., Lee, S. J.. 2025-11-14. Development of Recombinant Anti-TLR2 Antibodies and PLGA Nanoparticle-based Gene Therapy for the Treatment of Neuropathic Pain. https://doi.org/10.1101/2025.11.13.688281

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