Journal Article

Lipid nanoparticle delivery of siRNA to dorsal root ganglion neurons to treat pain

Chen, Dean Shuailin, Renthal, William, Zhou, Hui, Jain, Aakanksha, Zhang, Biyao, Shi, Jinjun, Cheng, Yu-Ting, Hu, Caleb, Song, Yudong, Yong, Hyo Jeong, Jiang, Xingya, Petrova, Veselina, Kim, Hyoung Woo, Barkai, Omer, Lirk, Philipp, Han, Xiangfei, Woolf, Clifford J

2025

Overview

Sensory neurons within the dorsal root ganglion (DRG) are the primary trigger of pain, relaying activity about noxious stimuli from the periphery to the central nervous system; however, targeting DRG neurons for pain management has remained a clinical challenge. Here, we demonstrate the use of lipid nanoparticles (LNPs) for effective intrathecal delivery of small interfering RNA (siRNA) to DRG neurons, achieving potent silencing of the transient receptor potential vanilloid 1 (TRPV1) ion channel that is predominantly expressed in nociceptor sensory neurons. This leads to a reversible interruption of heat-, capsaicin-, and inflammation-induced nociceptive conduction, as observed by behavioral outputs. Our work provides a proof-of-concept for intrathecal siRNA therapy as a novel and selective analgesic modality.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Analgesics / Capsaicin / Capsaicin receptors / Central nervous system / Dorsal root ganglia / Nanoparticles / Neuroscience / Pain perception / RNA-mediated interference / Sensory neurons / siRNA / Transient receptor potential proteins