Evidence map›Paper›PMID 41388560›Full record

ArticleBMC pharmacology & toxicology2025

A tissue-penetrably engineered deoxyribonuclease 1 to prevent nasal polyp formation in chronic rhinosinusitis.

Su-Bin Kwak, Roza Khalmuratova, Sang-Jin Kim, Hyun-Woo Shin, Jong-Wan Park

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Article in BMC pharmacology & toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Su-Bin Kwak *Department of Pharmacology, Seoul National University College of Medicine, Daehak-ro 103, Jongno-gu, Seoul, Korea.
Roza Khalmuratova *Department of Pharmacology, Seoul National University College of Medicine, Daehak-ro 103, Jongno-gu, Seoul, Korea.
Sang-Jin KimDepartment of Pharmacology, Seoul National University College of Medicine, Daehak-ro 103, Jongno-gu, Seoul, Korea.
Hyun-Woo ShinDepartment of Pharmacology, Seoul National University College of Medicine, Daehak-ro 103, Jongno-gu, Seoul, Korea. charlie@snu.ac.kr.
Jong-Wan ParkDepartment of Pharmacology, Seoul National University College of Medicine, Daehak-ro 103, Jongno-gu, Seoul, Korea. parkjw@snu.ac.kr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeutrophilic chronic rhinosinusitis (CRS) is characterized by persistent inflammation and often responds poorly to corticosteroid therapy. In this disease, neutrophil extracellular traps (NETs) are increasingly recognized as key mediators of mucosal damage and polypogenesis. The removal of NETs by deoxyribonuclease 1 could be a potential therapeutic approach to overcome steroid resistance in neutrophilic CRS. In this study, we established a mouse model of neutrophilic CRS and evaluated the effect of a genetically engineered deoxyribonuclease 1 'AR-CR8 Dnase1' on NETs and polyp formation in the mice.

methodsHuman neutrophils were isolated and treated with LPS to induce NET formation. An animal model for neutrophilic CRS and polyps was developed by intranasal administration of LPS and Staphylococcal toxin. H&E staining and immunofluorescence were performed to identify polyps, NETs, and immune cells in nasal cavities.

resultsAR-CR8 Dnase1 effectively degraded NET-like structures in LPS-stimulated human neutrophils. In the mouse CRS model, the intranasal administration of AR-CR8 Dnase1 noticeably reduced the burden of nasal polyps. The intranasal treatment of Dnase1 was effective as much as an injection of dexamethasone in reducing polyp number and NET accumulation in this model.

conclusionsThese results suggest that an engineered deoxyribonuclease 1 like AR-CR8 Dnase1 be an emerging bio-drug to inhibit inflammatory reaction and polyp formation in patients with neutrophilic CRS. AR-CR8 Dnase1 may be an alternative therapeutic for patients with CRS who are not suitable for steroid therapy, and further studies comparing dosing, durability, and safety are needed before considering clinical use.

trial registrationNot applicable.

Indexed as

Deoxyribonuclease INasal PolypsRhinitisSinusitisAdministration, IntranasalAnimalsChronic DiseaseDisease Models, AnimalExtracellular TrapsFemaleHumansLipopolysaccharidesMaleMiceMice, Inbred C57BLNeutrophilsDeoxyribonuclease ILipopolysaccharidesChronic rhinosinusitisDeoxyribonuclease 1Nasal polypNeutrophil extracellular trapsTissue-penetrating peptide

Identifiers

PMID41388560
PMCPMC12817691

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.