# This New CRISPR Technique Flips Genes Back On Without Touching DNA > Since its discovery, the CRISPR system has revolutionized biology by offering a relatively simple way to modify the genome. Its basic principle - Author: Maxime Marquette - Publisher: MadMax (https://mad-max.co) - Section: Reportage - Published: 2026-07-07 - Canonical URL: https://mad-max.co/en/article/cette-nouvelle-technique-crispr-rallume-des-genes-sans-jamais-toucher-l-adn ## Key takeaways - The classic CRISPR system uses molecular scissors, and every DNA cut risks repair errors, unwanted mutations and genomic instability. - The researchers used a catalytically inactive dCas9 protein, which acts only as a delivery vehicle for enzymes that remove or add methyl marks. - In human cells, removing the methyl marks reactivated a silent gene, and re-adding them silenced it again, which the authors present as direct proof of methylation's causal role. - The first target is sickle cell disease: reactivating the fetal globin gene in a patient's blood stem cells, which would be reinjected after editing. - Possible uses beyond sickle cell disease include certain cancers and fragile X syndrome, but all results so far come from lab experiments on cultured human cells, with animal tests and clinical trials still to come. ## Introduction: when cutting is no longer the only option ### Classic CRISPR and its Achilles' heel Since its discovery, the **CRISPR** system has revolutionized **biology** by offering a relatively simple way to modify the **genome**. Its basic principle relies on **molecular scissors**: a protein guided by a fragment of **RNA** cuts **DNA** at a precise spot, allowing a genetic sequence to be disabled, corrected, or inserted afterward. This method has enabled major therapeutic advances, but it carries an inherent risk: every cut in the **double helix** can lead to repair errors, **unwanted mutations**, or even longer-term genomic instability. It is precisely this Achilles' heel that a team of researchers from the **University of New South Wales**, working with **St Jude Children's Research Hospital** in Memphis, has just sidestepped with remarkable elegance. Published in **January 2026** in the journal **Nature Communications**, their study demonstrates that it is possible to wake up **silenced genes** without ever cutting the DNA strand, by targeting an entirely different level of **genetic regulation**. ### Chemical anchors instead of scissors The key to this breakthrough lies in a mechanism called **DNA methylation**. Small chemical tags, called **methyl groups**, attach to certain portions of the genome and act as **molecular anchors** that keep genes locked in an "off" position. For decades, the scientific community debated the following question: are these chemical marks the direct cause of **genetic silencing**, or are they merely a sign accompanying genes that are already inactive for other reasons? Professor **Merlin Crossley**, lead author of the study and **deputy vice-chancellor academic** at UNSW, sums up the discovery with a vivid image: removing these marks is like "clearing away the cobwebs," and the gene switches back on immediately, as though an invisible brake had been released. *What I love about this story is the almost childlike simplicity of the experiment that settled a scientific debate decades in the making: remove a chemical mark, the gene wakes up; put it back, the gene goes back to sleep. Sometimes the most solid proof comes from the clearest possible demonstration.* ## A scientific debate finally settled ### Remove, then reapply: proof by experiment To demonstrate that DNA methylation does not merely accompany **genetic silencing** but is in fact its direct cause, the team designed a **two-stage experiment**. First, researchers used a modified version of the **CRISPR** system, stripped of its cutting function, to deliver **enzymes** capable of removing the methyl groups from a target gene. The result: the silent gene resumed normal expression. Next, by adding the methyl marks back onto that same gene, the team observed its **silencing** return. This **full reversibility**, achieved in the lab on **human cells**, provides direct, not merely correlative, proof of methylation's causal role in gene silencing. Professor **Kate Quinlan**, co-author of the study, notes that this **epigenetic editing** approach can boost a gene's expression without ever altering the DNA sequence itself. According to her, therapies built on this technology should carry a reduced risk of unwanted side effects compared with the first and second generations of CRISPR tools, both of which rely on cutting the double helix. ### A tool called dCas, stripped of its scissors Technically, the system used relies on a **catalytically inactive** version of the **Cas9** protein, often called **dCas9**, which is unable to cut DNA. This protein acts purely as a **delivery vehicle**, guided by RNA to the precise location of the target gene, where it drops off an enzyme tasked with removing or adding **methylation** marks. This conceptual shift, from molecular scissors to a **targeted delivery** system, opens up an entirely new category of gene-editing tools, one that some researchers already describe as a **third generation** of genome editing. Unlike **first-generation** tools, which disable genes by cutting them, and **second-generation** tools, which correct individual letters of the genetic code, this epigenetic approach never touches the structure of the DNA itself. It acts only on its **accessibility**, somewhat like flipping a switch rather than rewiring the electrical circuit itself at a deeper level. *There is something reassuring about this idea of a switch rather than a pair of scissors. We often picture genetic modification as an irreversible, risky act, yet this technique introduces a form of reversibility that completely changes how we should perceive the risk tied to these therapies.* ## A first concrete application: sickle cell disease ### Waking a fetal gene in adults The first application envisioned by the Australian team concerns **sickle cell disease**, a **genetic blood disorder**. Every human being carries a **fetal globin gene**, which functions perfectly before birth by producing a healthy form of **hemoglobin**, before being naturally switched off shortly afterward. In people with sickle cell disease, the adult hemoglobin their bodies produce is **defective** and causes **red blood cells** to become misshapen. The researchers' idea is to reactivate this dormant fetal gene, rather than attempting to directly repair the adult gene responsible for the disease. The envisioned clinical scenario would work like this: draw a patient's blood stem cells, apply epigenetic editing in the lab to remove the methyl marks keeping the fetal globin gene switched off, then reinject these modified cells into the body. Once settled into the bone marrow, they could then produce healthier red blood cells, all without the patient's DNA sequence ever being cut or rewritten. ### Promise beyond sickle cell disease alone While sickle cell disease is the first target for this technology, its potential extends well beyond that single illness. Researchers point to possible applications for certain **cancers**, where the goal would be to reactivate **tumor suppressor genes** that have been silenced by methylation, or for **developmental disorders** such as **fragile X syndrome**, where a key gene is likewise switched off through this same epigenetic mechanism. The possibility of simply reversing a chemical mark, rather than rewriting an entire segment of the genome, opens up a considerable therapeutic field for many diseases that remain incurable today. All these experiments remain, for now, confined to the laboratory, carried out on cultured human cells at UNSW and in Memphis. The next steps planned by the team include tests in animal models, before moving, if the results hold up, toward human clinical trials. *What strikes me is this team's methodical caution: no premature announcement of a miracle cure, just a careful succession of validation steps. That is exactly the pace science should adopt when facing promises this significant for patients living with these diseases every day.* ## Why this approach changes the safety equation ### The risk of DNA cuts finally sidestepped Traditional CRISPR tools, whether fully disabling a gene or correcting a single mutation, almost always rely on creating a **double-strand break** in the DNA molecule. This process, while powerful, carries documented risks: imperfect repairs, unwanted insertions or deletions, chromosomal rearrangements, and in some cases disruptions that can favor the development of cancerous cells. These risks have always been a significant barrier to the large-scale use of gene therapies based on directly cutting DNA. By avoiding these cuts entirely, the epigenetic editing proposed by the Crossley and Quinlan team mechanically reduces this type of complication. Since the genetic sequence remains physically intact from start to finish of the treatment, the risk of accidental long-term mutations drops significantly, which could make it easier for these future therapies to gain regulatory and clinical acceptance among both patients and health authorities. ### A reversibility that changes the treatment philosophy Another major advantage of this approach is its **reversibility in principle**. Because the modification relies on adding or removing chemical marks, rather than permanently rewriting the genetic code, it becomes theoretically possible to undo an intervention if necessary, by reapplying enzymes capable of restoring the original methylation. This feature fundamentally sets this technology apart from classic genetic edits, which are generally designed to be permanent and irreversible once applied to a patient. This flexibility opens the door to a more adjustable form of genetic medicine, where a gene's expression could be fine-tuned as a patient's condition evolves, rather than fixed once and for all by a molecular-level surgical intervention. *We often talk about genetic medicine as a one-way street, with no possibility of turning back. This reversibility in principle completely changes the psychological equation, both for the researchers developing these treatments and for the patients who will one day have to decide whether to receive them.* ## Conclusion: a new generation of gene editing ### What this discovery confirms This study, led by **UNSW Sydney** and **St Jude Children's Research Hospital**, settles a long-standing scientific debate by demonstrating that DNA methylation directly causes the silencing of certain genes, rather than the other way around. More importantly, it proves that it is possible to act on this methylation with precision, using the CRISPR system not as scissors but as a targeted delivery tool for enzymes, without ever cutting the DNA molecule. The potential therapeutic implications, starting with **sickle cell disease**, still need to be confirmed through trials in animal models and then in humans. But the very principle behind this method marks an important step in the evolution of gene-editing tools, opening up a more cautious and potentially safer path than previous approaches. ### Still a long road to the clinic It is worth remembering that all these results currently come exclusively from laboratory experiments on cultured human cells. The move to animal models, and then to clinical trials, will take time and will need to confirm that the effects observed in the lab hold up in a complete living organism, with all the physiological complexity that implies. Even so, this advance illustrates how fundamental research in biology keeps generating ever finer, safer tools for treating genetic diseases that have, until now, resisted classic therapeutic approaches. This kind of progress also serves as a broader reminder of how science rarely advances through isolated, spectacular leaps. Most often it moves forward in small successive steps, with each research team building on the discoveries of those before it to refine a tool, resolve a technical detail, or lift a persistent uncertainty. Epigenetic editing is no exception to this rule: it builds on decades of research into DNA methylation and on the CRISPR tools themselves, before finally converging on this gentler, potentially safer approach for tomorrow's patients. **By Maxime Marquette, columnist** ## Columnist's transparency note ### Editorial stance I am not a journalist but a **columnist and analyst**. My expertise lies in observing and analysing the geopolitical, economic and strategic dynamics that shape our world. My work is to take political strategies apart, to understand global economic movements, to put the decisions of international actors in context and to offer analytical perspectives on the changes that are redefining our societies. I do not claim the cold objectivity of traditional journalism, which stops at reporting facts. **I claim analytical clarity**, rigorous interpretation and a deep understanding of the complex issues that concern us all. My role is to give meaning to the facts, to place them in their historical and strategic context, and to offer a critical reading of events. ### Method and sources This text keeps the basic distinction between **verified facts and interpretive analysis**. The rule never changes: a factual claim is published only when a verifiable source supports it, and the sources this article actually used are listed under **Sources**, never here. **Primary source families** used by the publication, when the story has them: official statements from governments and international institutions, public statements by political leaders, reports from intergovernmental organisations, dispatches from recognised international news agencies. **Secondary source families**: specialised publications, internationally recognised news media, analyses from established research institutions, reports from industry organisations. When an article cites statistical, economic or geopolitical data, it comes from the institutions that produce it (intergovernmental organisations, central banks, national statistics offices), and the exact institution is named under **Sources**. ### Nature of the analysis The analyses, interpretations and perspectives in the analytical sections of this article are a **critical, contextual synthesis** based on the information available, the trends observed and the expert comments cited in the sources consulted. My role is to interpret these facts, to set them in the context of today's geopolitical and economic dynamics, and to give them a coherent meaning within the larger story of the changes shaping our time. These analyses reflect expertise built through continuous observation of international affairs and an understanding of the strategic mechanisms that drive global actors. This article describes a documented state of affairs on its publication date, not a prediction: later developments may shift its outlook. No update is promised in advance; when an article is corrected or completed, the change is dated in the text. ## Sources ### Primary sources - ScienceDaily — This CRISPR breakthrough turns genes on without cutting DNA — January 2026 - Nature Communications — Removal of promoter CpG methylation by epigenome editing reverses HBG silencing — 2025 - UNSW Sydney — Research on epigenetic editing and the reactivation of silenced genes — January 2026 ### Secondary sources - Futura Sciences — Accessible analysis of advances in CRISPR epigenetic editing — 2026 - Sciences et Avenir — Coverage of innovations in gene therapy and CRISPR — 2026 - Amphi Sciences Ouest-France — Accessible coverage of research in molecular biology and genetics — 2026 --- Source: Maxime Marquette, MadMax. When citing, name the author and link https://mad-max.co/en/article/cette-nouvelle-technique-crispr-rallume-des-genes-sans-jamais-toucher-l-adn