Targeted epigenetic editing of SPDEF reduces mucus production in lung epithelial cells

This study aims to reduce lung epithelial mucus production by targeted silencing SPDEF using the novel strategy, epigenetic editing. Zinc fingers and CRISPR/dCas platforms were engineered to target repressors (KRAB, DNA methyltransferases, histone methyltransferases) to the SPDEF promoter. All constructs were able to effectively suppress both SPDEF mRNA and protein expression, which was accompanied by inhibition of downstream mucus-related genes [anterior gradient 2 (AGR2), mucin 5AC (MUC5AC)]. For the histone methyltransferase G9A, and not its mutant or other effectors, the obtained silencing was mitotically stable. These results indicate efficient SPDEF silencing and downregulation of mucus-related gene expression by epigenetic editing, in human lung epithelial cells. This opens avenues for epigenetic editing as a novel therapeutic strategy to induce long-lasting mucus inhibition.

Source: AJP: Lung Cellular and Molecular Physiology - February 28, 2017 Category: Respiratory Medicine Authors: Song, J., Cano-Rodriquez, D., Winkle, M., Gjaltema, R. A. F., Goubert, D., Jurkowski, T. P., Heijink, I. H., Rots, M. G., Hylkema, M. N. Tags: RESEARCH ARTICLE Source Type: research