A research study has demonstrated epigenetic gene editing as a therapeutic strategy to induce long-lasting mucus inhibition in patients with chronic inflammatory lung diseases.
Airway mucus hypersecretion is a pathophysiological feature of asthma and chronic lung diseases. The excess mucus production contributes to morbidity and mortality in many patients and therefore, reducing mucus production is crucial for improving patients’ quality of life. Mucus hypersecretion involves increased expression of mucin genes and increased mucin production and release. The transcription factor SAM-pointed domain-containing Ets-like factor (SPDEF) plays a critical role in the regulation of mucus production, and therefore represents a potential therapeutic target.
In the present study published in the American Journal of Physiology, a research team led by Prof. Machteld Hylkema of University of Groningen investigated the potential of targeted gene editing as a therapeutic strategy to inhibit mucus production in lung epithelial cells.
The team used zinc finger nuclease and CRISPR/Cas gene editing platforms to target and silence SPDEF promoter in human lung epithelial cells. Results showed that both the constructs could effectively suppress SPDEF mRNA and protein expression and this in turn resulted in the inhibition of downstream mucus-related genes.
Thus, the study indicate SPDEF silencing through epigenetic gene editing as a therapeutic strategy to induce long-lasting mucus inhibition in patients with chronic inflammatory lung diseases.
Source: Targeted epigenetic editing of SPDEF reduces mucus production in lung epithelial cells. Juan Song et al., American Journal of Physiology – Lung Cellular and Molecular Physiology December 2016. DOI