A DNA Tetrahedron-Delivered miR-17-5p mimic exerts dual anti-inflammatory and Anti-Pseudomonas aeruginosa effects in cystic fibrosis.

Authors

Yunfei Ye, YinHeRichard Sun, Hawraa Shahrour, Irene Oglesby, Yiran Zheng, Catherine M Greene

Published in

Non-coding RNA research. Volume 20. Pages 72-85. Epub Jul 29, 2026.

Abstract

Cystic Fibrosis (CF) is a genetic disease characterized by chronic pulmonary inflammation and infection, principally with Pseudomonas aeruginosa. P. aeruginosa can exhibit resistance to innate immune effectors and antibiotics by expressing virulence factors and forming antibiotic-resistant biofilms, which facilitate chronic infection in immunocompromised hosts. Therefore, new antimicrobials are required. MicroRNAs are mammalian short non-coding RNAs that negatively regulate protein expression. MiR-17-5p, an inhibitor of CXCL8/IL-8, can decrease neutrophil abundance in the CF lung. Here we investigate whether miR-17-5p has anti-P. aeruginosa properties. The sequences of the full-length miRNA and the miR-17-5p isoform miR.17.P4d_5p were tested for their ability to bind to RNA transcripts encoded by P. aeruginosa PAO1 (NC_002516) using the bioinformatics tools RocketmiR and IntaRNA. A miR-17-5p DNA tetrahedron (Td-miR.17.P4d_5p, Size = 118-180 nm) was tested for its delivery into CF bronchial epithelial cells and ability to inhibit IL-8 gene and protein expression, and its effects on P. aeruginosa growth, antimicrobial resistance, and biofilm formation. Successful delivery into CFBE41o- and 16HBE14o- cells inhibited IL-8 expression induced by Pseudomonas-conditioned medium (PAO1, Mucoid strains 1 and 2 p < 0.00001; PA14 p < 0.0001). Delivery into PAO1 and PA14 inhibited growth and biofilm formation while significantly enhancing their sensitivity to the antibiotic cefotaxime. Td-miR.17.P4d_5p also significantly inhibited biofilm formation in two clinical mucoid P. aeruginosa strains. qPCR and EMSA were used to investigate the mechanism of action of miR.17.P4d_5p. The data showed that miR.17.P4d_5p could inhibit expression of kynU (p < 0.00001), a tryptophan metabolism pathway molecule related to PAO1 growth, and the biofilm formation-related molecules pilL, fimX, ppkA and pslA (all p < 0.00001) in P. aeruginosa PAO1. The combined anti-IL-8 and anti-P. aeruginosa properties of miR.17.P4d_5p suggest its potential usefulness as a dual anti-infective and anti-inflammatory therapeutic strategy for CF.

PMID:
42571285
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.

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