Reacción a "Reactions: epigenetic editing technique lowers cholesterol in mice without altering DNA"

The study by Angelo Lombardo's group demonstrates for the first time that a single treatment using an epigenetic silencing strategy can specifically reduce the expression of a gene in a mouse model for almost a year without modifying the genome of the cell. In this case, the gene that is repressed is the Psck9 gene, which allows the reduction of cholesterol levels, but a similar strategy could be used to repress other genes.  

The study also shows that the modification is stable even when the cells divide, demonstrating that a single treatment would be sufficient to repress gene expression.  

The advantage over previously developed gene editing systems is that it does not require genome modification, which in principle makes it safer, which is particularly relevant when several genes are to be modified at the same time.  

Another major advantage of this system is that it can in principle be reversible by drug treatments or by using editors that, unlike in this work, allow gene activation, thus making it possible to switch a gene on or off as needed, as has been demonstrated in cell lines previously. 

However, it is important to note that this work demonstrates the possibility of stably repressing gene expression in vivo, but the ability to reverse the effect in vivo has not yet been studied, although it would be expected to be similar to that observed in previous studies in cultured cells.

The main novelty of this work is, therefore, the demonstration that this strategy allows the long-term repression of a gene in vivo without modifying the genome of the cell, reducing in principle the potential risks compared to conventional editing systems that generate modifications in the genome. 

If the results are confirmed in human cells in vivo, it could have an application for the future treatment of various diseases. Of course, it will be necessary to analyse in detail for each gene to be repressed the absence of non-specific activity.