Neutrophil elastase promoter (ELANE promoter)

The Neutrophil elastase promoter is the regulatory DNA sequence located upstream of the ELANE gene, which encodes the serine protease neutrophil elastase. It contains critical cis-regulatory elements, such as the TATA box (Goldberg-Hognes box), which are essential for the recruitment of RNA polymerase II and the initiation of transcription. In patients with severe congenital neutropenia (SCN), various mutations in the ELANE gene lead to the production of misfolded proteins that trigger the unfolded protein response (UPR) and apoptosis in neutrophil precursors. Recent therapeutic strategies, including the MILESTONE and PRECISE platforms, specifically target the ELANE promoter using CRISPR-Cas9 nickases or adenine base editors to inhibit gene expression. By suppressing the production of the toxic mutant elastase, these gene-editing approaches aim to restore normal neutrophil development and provide a universal curative treatment for SCN regardless of the specific mutation present in the coding sequence.

Other names

ELANE TATA boxELA2 promoterNeutrophil elastase regulatory regionGoldberg-Hognes box of ELANE

Transcriptional inhibition via targeted disruption of the TATA box sequence to prevent RNA polymerase II binding and mRNA expression.