Antisense-directed isoform switching of TRPV1 achieves long-lasting analgesia without thermoregulatory deficits

Published: 10 September 2026| Version 2 | DOI: 10.17632/32sty5g3w7.2
Contributor:
Qingyue Fu

Description

Raw Data for "Long-lasting analgesia by antisense-mediated switching of TRPV1 isoforms" Abstract:Chronic pain affects approximately 20-25% of the global population, yet existing treatments offer insufficient relief or pose significant safety risks. TRPV1 is fundamental to pain transmission. Conversely, its exon 7-skipped isoform TRPV1b is intrinsically insensitive to noxious stimuli. Here, we used a splice-switching strategy to suppress TRPV1 while simultaneously increasing TRPV1b expression. Stepwise screening of 172 antisense oligonucleotides (ASOs) identified a bipartite ASO that efficiently promoted TRPV1 exon 7 skipping in cultured cells and mouse tissues. Intracerebroventricular administration of this ASO elevated basal pain thresholds and produced long-term analgesia in mouse models of neuropathic, inflammatory, and cancer pain without causing motor or thermoregulatory deficits, or toxicity. Mechanistically, TRPV1b forms hetero-oligomers with full-length TRPV1, exerting a dominant-negative effect that attenuates agonist-evoked Ca²⁺ influx and channel activation. These findings demonstrate that ASO-directed splicing modulation can successfully bypass classical on-target toxicities, introducing a novel paradigm of target-specific pre-mRNA reprogramming for chronic pain intervention. Keywords: chronic pain; nociception; TRPV1; TRPV1b; antisense oligonucleotide; RNA splicing; exon skipping; analgesia. Data Structure and Content: The dataset is organized into 11 primary folders corresponding to Figure 1, 2, 5, and S1-8. Each folder contains original uncropped RT-PCR and Western blot images. Experimental Conditions: For detailed experimental protocols associated with these images, please refer to the "STAR methods" section of the main manuscript.

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Analgesia, RNA Splicing, Chronic Pain, Antisense Oligonucleotide

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