It's all just talk

Several studies discovered serious problems with CRISPR and cast the therapeutic potential of the gene-editing tech in doubt. In June, two studies published in Nature Medicine demonstrated that cells altered with CRISPR may be missing key anti-cancer mechanisms, increasing the risk that those cells will initiate tumors.

"We found that changes in the DNA have been seriously underestimated before now"

CRISPR uses an enzyme called Cas9 to excise small portions of DNA and introduce genetic changes at that location. The core element of the CRISPR system is a small piece of RNA that binds to a specific DNA sequence in a genome and the Cas9 enzyme. Once the RNA is bound to the DNA sequence, Cas9 cuts the DNA at the targeted location and the cell’s natural DNA repair mechanisms work to repair the DNA sequence.

Yet as Bradley and his colleagues discovered through a systematic study of human and mouse cells modified by CRISPR, this cellular repair process introduces a lot of errors—deletions and the scrambling of genetic code—to the DNA during the repair process. The reason that these extensive mutations had been overlooked in previous CRISPR research is because the errors often occur far from the site that was edited by CRISPR.

"Once we realized the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines and showed that the CRISPR-Cas9 effects held true"

These mutations can cause important genes to be turned on or off, such as genetic anti-cancer mechanisms. This poses serious problems for CRISPR as a therapy, which has already been used on 86 people in China and is under consideration for humans in the US. Moreover, because these mutations occur so far away from the gene editing site, they are difficult to detect with standard genotyping methods used to determine whether a CRISPR edit was successful.