ValiPharma's GeneICE technology enables the selective silencing of specific genes in humans and animals by targeted histone deacetylation leading to chromatin condensation.

ValiPharma is developing novel GeneICE drugs based on this principle

Active genes have an open chromatin structure that facilitates access to transcription factors for protein production. Condensation of the chromatin structure prevents access and silences gene expression.

Chromatin condensation is in turn controlled by the chemical state of the histone proteins associated with a gene. Acetylation of histone proteins leads to an open chromatin structure. Conversely, histone deacetylation causes chromatin to adopt a condensed structure and prevents gene expression.

GeneICE — how it works

In nature histone deacetylation of a particular gene is brought about by recruitment of a histone deacetylase complex (HDAC) to the gene. GeneICE mimics this natural mechanism by the delivery to the nucleus of a 2 module construct comprising:

1. a sequence specific DNA binding module that binds selectively to the gene of interest. This can be targeted to the gene promoter, the transcription start site or elsewhere in the primary transcript.
2. a gene repression peptide that recruits HDAC to the gene.

Binding of the GeneICE construct to its target gene leads to deacetylation of the histones associated with the gene, localised chromatin condensation and gene silencing.