Vector-free intra-airway in vivo epigenetic editing

Targeted epigenetic editing enables promoter-specific removal of DNA methylation marks and is emerging as a promising experimental and therapeutic strategy. 

Demethylation restores context dependent, adaptive enhancement of stimulated transcriptional responsiveness of intrinsic genes in situ.

Progress in vivo and translation to humans are hampered by the reliance on complex gene-incorporation strategies or cumbersome delivery tools to place an epigenetic editor construct into cells.

The researchers describe recombinant fusion proteins for the targeted demethylation of a gene, which do not require transgenesis, vectors, or packaging tools.

Results demonstrate intranuclear arrival of the epigenetic editors in vitro and in mouse lungs after intra-airway administration, localized DNA demethylation, and resulting highly specific derepression of the transcriptional response of a target gene.

https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(25)00173-8

https://sciencemission.com/Vector-free-intra-airway-epigenetic-editing