Within the cell, DNA is packaged into a structure known as chromatin, which can be divided into euchromatin and heterochromatin. The former consists of accessible 'open' DNA, and the latter of compact 'closed' DNA. A research team led by Professor Huimin Zhao from the University of Illinois, compared how two different approaches to genome editing – CRISPR/Cas9 and TALENs – deal with editing DNA in euchromatin and heterochromatin. The study, found that TALENs-mediated genome editing is up to five times more efficient than CRISPR/Cas9 mediated genome editing, when it comes to modifying heterochromatin. The reverse was true for euchromatin.
'We found that CRISPR works better in the less-tightly wound regions of the genome, but TALENs can access those genes in the heterochromatin region better than CRISPR,' said Professor Zhao. 'We also saw that TALENs can have higher editing efficiency than CRISPR. It can cut the DNA and then make changes more efficiently than CRISPR.'
CRISPR/Cas9 and TALENs both act as 'molecular scissors', cutting a target DNA region, which can then be repaired by the cell, potentially incorporating desired DNA modifications. The two methods differ in the way that they find, and cut, their target DNA. In the study, the researchers monitored how the two different methods search for and find their target site using single molecule fluorescence microscopy, and examined how efficient each method was at finding and cutting sites either within euchromatin, or heterochromatin.
Certain genetic disorders, including Fragile X syndrome, and sickle cell anaemia, are due to defects in heterochromatin regions. In the future, if genome editing becomes mainstream, it will be important to be able to target these regions as well as the genes in euchromatin. Indeed, TALENs, unlike CRISPR/Cas9, have also recently been shown to work on mitochondrial DNA – meaning they could also be used to target genetic disease due to mitochondrial defects (see BioNews 1055).
The study, published in Nature Communications, adds to the evidence that a broader selection of genome editing tools is needed to target all parts of the genome, said Professor Zhao.