Scientists have now created a new method of using CRISPR genome editing, which would allow them to activate genetics without breaking the DNA. It could potentially be a major improvement in using gene editing techniques to treat human diseases. Currently, most of the CRISPR systems work by creating DSBs or Double strand Breaks in regions of the genome targeted for editing. Many scientists and researchers have opposed creating breaks in the DNA of living humans. So the Salk group tried their new method to treat diseases such as diabetes, kidney disease, and muscular dystrophy in the mouse models.
CRISPR has proved to be a powerful tool for gene therapy, but there are still many concerns regarding some mutations generated by the DSBs though the Salk group is able to get around that concern. Originally, Cas9 enzyme couples with guide RNA to create DSBs. But just recently, researchers have used a dead form of dcas9 to stop the cutting of DNA. DCas9 would couple with transcriptional activation domains, that turn on targeted genes. But it is still difficult to be used in clinical applications.
Salk group team combined dcas9 with bunch of activator switches to uncover a combination that would work even when the proteins are not fused with one another. These components all work together to influence endogenous genes. It would influence genetic activities without having to change the DNA sequence.
In order to prove the usefulness of this method, scientists used mouse models of acute kidney disease, type 1 diabetes, and a form of muscular dystrophy. They engineered their new CRISPR system to boost the expression of an endogenous gene that would reverse the symptoms of the disease. In all three cases, they reversed disease symptoms.
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Photo credit: Martyn Fletcher