Scientists have discovered a genome editing technique that could one day be put to treat conditions like progeria and Huntington’s disease.
In research published in Cell Research, the authors described a tool named SATI, a variant of the CRISPR approach to genome editing. Unlike its predecessors, SATI allows alterations of a wider array of mutations in more cell-types. It offers the possibility of treating genetic conditions that were earlier thought to be intractable.
‘This study has shown that SATI is a powerful tool for genome editing,’ said Professor Juan Carlos Izpisua Belmonte at the Salk Institute in La Jolla, California, a lead study author. ‘It could demonstrate instrumental ineffective strategies for target-gene replacement of many different types of mutations, and opens the entryway for utilizing genome-editing apparatuses to perhaps fix an expansive scope of hereditary maladies.’
SATI is a gene ‘knock-in’ method. It means that it works by putting a normal copy of a mutated gene in the noncoding DNA before the site of the problem gene. This indicates that the new gene can produce the functional proteins the cell requires alongside the mutated gene and that it can help relieve symptoms without needing to fully replace a problematic gene.
To test the working of SATI, the researchers observed mice harboring a mutation in the LMNA gene that can lead to a premature aging syndrome called progeria in mice and humans alike. They infused newborn mice with a healthy portion of the gene, which substituted the broken partner by exploiting the DNA fix apparatus found inside cells.
The treated mice not only had a higher lifespan but also showed an improvement in general health and body function. The researchers discovered very few instances of off-target effects in unintended sections of the genome, which is a worry when using genome editing inside the body.
Improvement of symptoms was clearly observed when SATI was performed in adult mice with progeria. The researchers told that this is an indication of the utility of the technique, as many genetic diseases are diagnosed later in life.
Contrary to earlier methods, SATI could edit the genes within both dividing and non-dividing cells with similar efficiency as it is able to use a variety of DNA repair machinery.
Although the mice showed an improvement in symptoms of progeria, only a tiny and sometimes undetectable populations of cells were edited by the SATI with success. The researchers now aim to develop the technique further to increase its efficiency.
‘In particular, we will examine the details of the cell frameworks engaged with DNA fix to refine the SATI innovation much further for better DNA revision,’ said Dr. Reyna Hernandez-Benitez, additionally at Salk, and co-first author on the paper.
