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Updated: Aug 5, 2026
Development of Recombinant Proteins to Treat Chronic Pain
Published on: April 11, 2018
Development of recombinant anti-TLR2 antibodies and PLGA nanoparticle-based gene therapy for the treatment of
Subeen Lee1, Jaekyung Jeon2, Hyunji Lee2
1Interdisciplinary Program in Neuroscience, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea.
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 antibodies 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.
Insights
This study introduces a novel gene therapy using nanoparticles to deliver anti-Toll-like receptor 2 (TLR2) antibody genes. This approach offers sustained pain relief and reduced neuroinflammation in neuropathic pain models.
Area of Science:
- Neuroscience
- Immunology
- Biotechnology
Background:
- Neuroinflammation, particularly involving microglial Toll-like receptor 2 (TLR2), drives neuropathic pain.
- Current TLR2-targeting antibodies face challenges with central nervous system delivery and efficacy duration.
Purpose of the Study:
- To develop a non-viral gene therapy for sustained expression of anti-TLR2 antibodies in the central nervous system.
- To evaluate the efficacy of this gene therapy in treating neuropathic pain.
Main Methods:
- Utilized biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for gene delivery.
- Selected high-affinity nanobodies and single-chain variable fragments targeting TLR2 via phage display.
- Administered PLGA NP-encapsulated antibody genes intrathecally in mouse models of neuropathic pain.
Main Results:
- Demonstrated suppression of TLR2-dependent signaling in vitro and in vivo.
- Achieved robust and sustained analgesia following a single intrathecal administration.
- Observed reduced glial activation and proinflammatory cytokine expression in treated mice.
Conclusions:
- Established a modular nanoparticle-based platform for sustained antibody expression within the central nervous system.
- Showcased the potential of this gene therapy for treating chronic pain associated with innate immune activation.
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