Some of our most touted advancements in weaponry involve ‘surgical strike capabilities’, the idea being that the more precisely you attack a specific target, the less unintended damage there will be. Recent innovations in genome editing, such as CRISPRs and TALENs, may provide researchers with an improved genomic targeting system, enabling more precise aiming towards specific loci while preventing unintended mutations to the rest of the genome.
Adrian Veres and his team investigated recently put whole genome sequencing to work in human pluripotent stem cell clones in an effort to see what level of collateral damage the specialized nuclease tools CRISPR-Cas9 systems and TALENs may introduce to the genome of human pluripotent stem cells.
They did find a few off-target mutations, but the incidence of them was very low. Here are a few other key findings they discovered along the way:
- While the clones did not seem to have nuclease specific mutations, they were no longer isogenic to their parent cells because they had undergone mutations during clonal expansion.
- The team pointed out that while they used WGS to achieve ~60x coverage, this method isn’t precise enough to find many of these unintended genomic changes. They feel that a more exact method that can determine the what, if any, collateral damage is introduced during genome editing would be more telling.
- While the researchers concluded that some cells could undergo unintended alterations, it did not seem to be a great enough risk to be a concern in disease modeling.
For more information, please train your sights to Cell Stem Cell (July 2014)