Legacy Errors
CRISPR-Cas9 is an effective tool for modifying the genome of microorganisms, as well as animals and plants. In healthcare, this method creates opportunities for the treatment of numerous genetic diseases, provided that the DNA is modified correctly and does not undergo undesirable changes. To date, such mutations have been studied on cell lines, but there is not enough information about the consequences at the body level.
In a new study, Adam Amur and his group from Uppsala University found that this method leads to unforeseen changes in DNA that can be inherited by the next generation.
As part of this project, researchers studied the effect of CRISPR-Cas9 embryos of aquarium fish danio rerio. Since DNA molecules and their mechanisms are the same in all animals, the results can be transferred to humans.
The researchers edited the danio embryos using four guide RNAs pointing "genetic scissors" at the target site. After that, they sequenced the DNA of more than 1,100 eggs, fry and adult fish in two generations and found that structural variations (SV), i.e. large insertions or deletions (more than 50 pairs of nitrogenous bases), accounted for 6% of the results of embryo editing. These SVS also occurred on non-targeted DNA sites. In addition, 26% of offspring from adults grown from edited embryos carry a non-target mutation outside the target gene and 9% – SV.
The ability of unwanted mutations and changes in larger DNA regions accompanying embryo editing with CRISPR-Cas9 to be inherited by the next generations may have long-term unintended consequences. Therefore, scientists call for caution and thorough testing before using CRISPR-Cas9 for medical purposes.
Article I.Höijer et al. CRISPR-Cas9 induces large structural variations at on-target and off-target sites in vivo that segregate across generations is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Uppsala University: CRISPR-Cas9 can generate unexpected, heritable mutations.