Our genes play a huge role in who we are, but they aren’t the full story.

For instance, think about any identical twins you may know. Some pairs of twins are perfect lookalikes, while other identical twins may be different heights or have different face shapes. A big contributor to why two people with identical DNA can look quite different is epigenetics.

The epigenome is a naturally occurring system for controlling gene expression. It is ubiquitous, found in every human cell in the form of chemical tags along the chromatin. The epigenome is what determines which genes are expressed and at what levels. Unlike the genetic code itself, which is largely permanent and identical between all cells, epigenetic markers are dynamic from one tissue to another and one moment to the next.

Control of the epigenome therefore presents enormous therapeutic promise for changing the activity of cells, without making permanent edits to their DNA.

Epigenetic editing explained

Epigenetic editing to control gene expression

At Epic Bio we are advancing a flexible therapeutic approach that can dial up or down gene expression without permanently altering the DNA. We call our platform the Gene Expression Modulation System (GEMS).

GEMS constructs are mutation-agnostic (since they target genes’ regulatory regions) and can fine-tune transcription in an infinite number of ways.

Each construct has three basic components: 1) a DNA-binding protein, 2) one or more guide RNAs, and 3) one or more modulators.

When paired with a custom guide RNA, the DNA-binding protein recognizes and binds to the target sequence. From there, modulators can customize the gene’s expression in myriad ways, including activating or repressing transcription of the gene, or adding or removing epigenetic markers to the gene locus.

Programmable potential of modulators

The activities of transcriptional and epigenetic modulators identified to date range from transient to long-lasting, subtle to strong, and small-scale to large-scale in their effects on enhancing or diminishing gene transcription. By stringing together multiple modulators in one GEMS construct, it is possible to engineer even more specific effects upon the target gene.

Histone modulators, activating

Modulators designed to catalyze removal or addition of methyl or acetyl groups on histones can activate the expression of the targeted genes.

Transcriptional activators

Modulators designed to amplify a gene’s rate of transcription can directly increase its expression.

Histone modulators, repressing

Modulators designed to catalyze removal or addition of methyl or acetyl groups on histones can repress the expression of the targeted genes.

Transcriptional repressors

Modulators designed to reduce a gene’s rate of transcription can directly decrease its expression.

Further reading