Kobe University researchers succeed in developing ‘Target-Aid’, a technique that doesn’t cleave DNA
Genome editing is a technique which can directly manipulate the genome information of various organisms without leaving an artificial strand. It has seen rapid progress in recent years and is gradually becoming a revolutionary tool in fields ranging from life sciences to advanced medical research.
Known to be highly effective, genome editing using artificial nuclease aims to cut the DNA at the target point and to modify the gene while it is repaired. Artificial nuclease is an enzyme artificially designed for recognizing and cutting arbitrary sequence of DNA strand. As this method is efficacious in biological materials for which genetic operation was difficult, it has been used mainly for higher eukaryotes such as animals and plants.
However, a major issue with this method has been the uncertainty of inducing the intended mutation and cytotoxicity caused by splitting of chromosomes (the quality of causing cell death or functional disorder within cells).
Now, researchers demonstrated that it is possible to modify genetic function by inducing target ‘point mutation’ at a highly efficient rate.
A team involving Kobe University researchers has succeeded in developing ‘Target-AID’, a genome
editing technique that does not cleave the DNA. The technique offers, through high-level editing operation, a method to address the existing issues of genome editing.The researchers induced point mutations by forming a synthetic complex through removal of nuclease activity from the CRISPR system through artificial nuclease and addition of deaminase, a deaminizing (base-modifying) enzyme, and then expressing it in yeasts and mammalian cells. Later, they confirmed that, compared to previous nuclease models, cytotoxicity reduced significantly when the DNA was modified without cutting.
This technique is capable of doing a more diverse, higher-level genome editing operation as it can efficiently conduct intended modification in a way that does not put significant burden on the cells. It is expected that the new technique will be applied to gene therapy in the future in addition to providing a powerful tool for breeding useful organisms and conducting disease and drug-discovery research.
