CRISPR-Based Editing Reactivates Genes Without DNA Cuts

Researchers at UNSW Sydney and St Jude Children’s Research Hospital have demonstrated a CRISPR-based method that reactivates genes without cutting DNA, according to findings published in Nature Communications.

This approach is designed to remove DNA methylation marks, which are chemical tags that silence genes, using a modified CRISPR system to deliver enzymes that erase these marks while avoiding DNA strand breaks.

The study confirmed that DNA methylation directly influences whether genes are active or inactive. When methyl groups were removed, genes became active, and when methyl groups were restored, gene activity was silenced again.

Laboratory experiments were conducted using human cells, focusing on reactivating the fetal globin gene. This gene reactivation in vitro may present a potential therapeutic strategy for conditions such as Sickle Cell disease.

What the numbers show

• The research was published in Nature Communications in December 2025
• Experiments were performed in vitro using human cells
• The study involved teams from UNSW Sydney and St Jude Children’s Research Hospital

The technique relies on a CRISPR system that targets methyl groups without introducing breaks in the DNA. Enzymes delivered by the system remove these chemical tags, allowing for gene reactivation without altering the underlying genetic sequence.

Other CRISPR-based technologies, such as CRISPR activation (CRISPRa), also increase gene expression without changing the DNA sequence. CRISPRa uses a catalytically inactive Cas9 fused to activator proteins, while prime editing can introduce new genetic information without causing double-strand breaks.

CRISPR gene editing can also regulate gene expression by using dead Cas9 proteins fused to regulatory factors, offering additional methods for modulating genes without cutting DNA. These approaches expand the range of gene regulation tools available for research and potential therapies.

The research team stated that future plans include testing the epigenetic editing method in animal models and developing additional CRISPR-based tools. These next steps aim to further explore the technique’s applications and effectiveness in broader biological contexts.

* This article is based on publicly available information at the time of writing.