Two recently published studies cited two types of CRISPR gene editors that change individual bases in the DNA of mouse embryos and rice plants. While one of these worked as normal, the other introduced unintended mutations, making edits in the wrong places.
If one doesn’t already know what it is, CRISPR is a gene editing tool that can alter DNA sequences and modify gene functions. These “genetic scissors” are easy to use and are more efficient than than the previous genome-editor, TALENS. In particular, the CAS 9 enzyme allows for CRISPR to work the way it does. Recently, scientists demonstrated that CRISPR can be used to fix human genetic defects such as cystic fibrosis and cataracts in animal models.
Back to the topic at the hand, the study created an experiment to test how many accidental edits were made by three different CRISPR editors. After injecting one of the two mouse early-stage embryo cells with a CRISPR editor, the researchers used a genetic trick that made all cells that received the editor glow the color red. They separated the edited cells and the unedited cells before deciphering both of the groups.
Two of the gene editors, the CRISPR CAS9 as well as a base editor that changes adenine to cytosine, didn’t cause any more mutations than unedited cells. For the CRISPR CAS9 editor, this means that that the CAS9 enzyme were making cuts as intended. However, the base editor that changes cytosine to thymine caused 20 times more mutations than that of unedited cells. According to David Liu, a chemical biologist whose team created the two base editors, the cytosine changing enzyme can “grab single-stranded DNA that it gets close and make edits on its own.” The tighter these cytosine base enzymes bind to the DNA, the more likely the editor can introduce mistakes into the DNA.
Obviously, these editors need revising and improvement. “The community needs these worst-case scenario pressure tests so we can make sure there’s a good margin of safety when these agents do enter clinical trials,” says David Liu. He then assures that “newer versions of the cytosine base editors don’t bind to DNA as tightly” and that “more recent versions will produce fewer typos.”