Neutrophil elastase (ELANE) mutant allele genomic DNA (ELANE mutant DNA)

The mutant ELANE allele genomic DNA at SNP-linked loci is a precision therapeutic target for treating severe congenital neutropenia (SCN) and cyclic neutropenia. Mutations in the ELANE gene, which encodes the enzyme neutrophil elastase, lead to the production of misfolded proteins that trigger endoplasmic reticulum (ER) stress and the unfolded protein response, causing the death of developing neutrophils in the bone marrow (Horwitz et al., 2013). Because these mutations typically act through a toxic gain-of-function mechanism, therapeutic strategies aim to selectively silence or disrupt the mutant allele while leaving the healthy wild-type allele intact. By targeting single nucleotide polymorphisms (SNPs) that are genetically linked to the mutation, gene-editing tools like CRISPR/Cas9 can distinguish between the two alleles with high precision (Nasri et al., 2020). This allele-specific approach is vital for restoring normal granulopoiesis and increasing the absolute neutrophil count in patients, thereby reducing their susceptibility to life-threatening infections (Tran et al., 2020). Current research is focused on utilizing this target to develop permanent, curative gene therapies that could replace the need for daily G-CSF injections or risky bone marrow transplants (Dale et al., 2017).

Other names

ELANEELA2Neutrophil elastase geneSCN1Cyclic neutropenia geneNeutrophil elastase-encoding gene

Allele-specific gene disruption or knockout to prevent the expression of toxic misfolded proteins while maintaining wild-type allele function.