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

delete2026-07-29
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PRE
AI
S
Subeen Lee
J
Jaekyung Jeon
H
Hyunji Lee
E
Ellane Eda Barcelon
J
Jinpyo Hong *
S
Sung Joong Lee *
DOI:10.1016/j.ymthe.2026.07.046delete
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Abstract

Abstract

En 中文
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.

Journal

Molecular Therapy cover
Molecular Therapy
IF:
12
Papers:
9.9K
Citations:
3.0W

Organization

O
oatc research center for neurodiseases
Scholars:
4
Papers: 1
Citations: 0
S
seoul national university
Scholars:
5.3K
Papers: 2.0K
Citations: 0
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