Imagine a surgeon performing a highly complex operation but unable to see the result of their actions. They carry out the intervention and then have to wait for an analysis to find out whether they hit the target precisely. For a long time, gene editing looked much the same: a molecular tool was introduced into a cell, and the effectiveness of its work was assessed only after the fact.
This task is especially difficult in mitochondria—tiny energy-producing structures of the cell that possess their own DNA. Mutations in the mitochondrial genome can lead to severe metabolic and neuromuscular diseases. Scientists have already learned how to target specific regions of mtDNA, but the result usually has to be verified through subsequent molecular analysis and sequencing.
Researchers from Zhengzhou University have proposed making this hidden process visible. In a study published in 2026 in CCS Chemistry , they presented a nanosystem that links the efficiency of gene editing to a fluorescent signal. In other words, a molecular event inside the cell gets a kind of light indicator.
The system is based on the protein Cas12a. After recognizing a specific DNA sequence, it becomes activated and begins to cleave special reporter molecules. Their cleavage generates a fluorescent signal that can be detected. Instead of waiting for a final analysis, the researcher can observe editing-related changes directly in a living system.
The main engineering challenge is delivering this entire molecular construct to mitochondrial DNA. For this purpose, DNA nanostructures formed via rolling circle amplification (rolling circle amplification, RCA) are used. They allow the necessary components to be assembled together while also reducing background signal.
This technology did not emerge from nowhere. In 2023, the same research line led to the creation of the InCasor system, described in Nature Communications. It already allowed visualization of specific mitochondrial DNA mutations in living cells and in experimental animals. Now the task becomes more complex: to see not only the presence of a genetic target but also to assess the effectiveness of the intervention itself.
The significance of such an approach can be particularly illustrated with a mitochondrial disease. In a single cell, there can be hundreds or thousands of copies of mtDNA: some normal, some mutant. Suppose a molecular tool is supposed to reduce the proportion of the dangerous variant. It is not enough to simply know that it “worked somewhere.” One needs to understand how much the ratio of normal to mutant DNA has changed, where this happened, and how the process develops over time. This is where the ability to observe molecular changes in a living system becomes especially valuable.
Treating patients with such nanosystems is still far off. Their safety, specificity, delivery to different tissues, and the risk of unintended effects need to be verified. But the very idea changes the approach to gene therapy: a molecular tool should not only perform its job but also leave the researcher with a clear signal of what has happened.
Gene editing is becoming not just more precise. For the first time, we are approaching the possibility of seeing its work from within—almost at the moment it occurs.
