// Oct 2026
How Can Epigenetic Editing Regulate Genes Without Changing DNA?
Epigenetic editing can regulate genes without changing DNA by using programmable DNA-binding systems to recruit activator or repressor machinery to specific genomic sites, tuning gene expression up or down while leaving the underlying sequence intact.
Epigenetic Editing Tunes Expression Without Cutting or Rewriting DNA
Many diseases are driven by abnormal gene activation or silencing. Epigenetic editing offers a way to address those diseases by regulating expression at the gene level without permanently altering the genetic code.
At ElevateBio, we are developing an RNA-guided epigenetic editing platform designed to program both gene activation and repression. This approach adds a controllable layer of gene modulation between transient gene expression and permanent DNA editing.
Repression Can Be Durable After Transient Delivery
Gene repression must be strong enough to reduce target expression and durable enough to have biological relevance after delivery. ElevateBio’s epigenetic repressors demonstrate B2M repression across multiple human cell types, including HEK293T cells, Jurkat cells, and primary human T cells (see full poster and all data).
In Jurkat cells, B2M repression persisted for at least four weeks after transient mRNA delivery. That result supports the potential for lasting gene expression changes without permanent DNA modification.
Activation Can Be Tuned to Physiologically Relevant Levels
Some diseases may benefit from restoring gene expression by only two- or three-fold, which requires tunability rather than maximal overexpression. Full overexpression can overshoot the desired biological range.
Across the platform, we demonstrate CD25 activation in Jurkat cells, activation of a metabolic gene target in mouse liver cells, and tunable activation of neurodevelopmental genes in Neuro2a cells.
Multiplexing Enables More Flexible Gene Control
Many diseases are not driven by a single gene moving in one direction. A useful epigenetic editing platform must be able to activate one target while repressing another.
ElevateBio’s platform includes distinct RNA-guided DNA-binding systems that support simultaneous regulation of multiple targets. In our studies, we activated CD25 while repressing B2M within the same Jurkat cell population.
Specificity and Delivery Optionality Matter
Precise gene regulation depends on on-target activity and delivery flexibility. In RNA-seq analysis, the intended target remained the dominant signal, with little to no detectable off-target transcriptional activity under the tested conditions.
In addition to mRNA delivery, ElevateBio’s compact epigenetic activators were packaged into an all-in-one AAV vector. Using CD25 activation as a readout, we confirmed functional AAV delivery in Jurkat cells.
Epigenetic Editing Expands the Gene Modulation Design Space
Epigenetic editing offers a programmable way to regulate gene expression without cutting or rewriting DNA. By enabling durable repression, tunable activation, multiplexed regulation, high on-target specificity, and multiple delivery strategies, ElevateBio’s platform expands the therapeutic design space for diseases driven by abnormal gene expression.
In the end, not every genetic disease requires permanent DNA editing. When the goal is to restore, reduce, or rebalance gene expression, epigenetic editing creates a flexible approach to gene control.
Ryan Rickels, PhD
Ryan Rickels, PhD, is a Senior Scientist in the Technology Department within ElevateBio’s Gene Editing Services, where he leads a small team focused on developing next-generation editing technologies and enabling their application across therapeutic programs.
Since joining ElevateBio in 2022, Ryan has played a key role in advancing multiple editing modalities, including base editors, reverse transcriptase (RT) editors, and epigenetic editors, helping drive innovation across ElevateBio’s gene editing portfolio.
Before joining ElevateBio, Ryan completed a postdoctoral fellowship at Duke University, where he focused on genome engineering technologies and their therapeutic applications. He earned his PhD from Northwestern University Feinberg School of Medicine, where his research centered on epigenetics and chromatin biology. Ryan received a B.S. in Biochemistry and Molecular Biology from the University of Tennessee.
Outside of work, Ryan enjoys exercising, camping, and spending time with his children.
