Research study stating that a novel technology for genome editing; a broad range of mutations in live organisms. The ability to edit genes in living organisms offers the opportunity to treat a plethora of inherited diseases. However, many types of gene-editing tools are unable to target critical areas of DNA, and creating such a technology has been difficult as living tissue contains diverse types of cells.
But researchers have developing a new tool dubbed SATI to edit the mouse genome; enabling the team to target a broad range of mutations and cell types. This study has shown that SATI is a powerful tool for genome editing. It could prove instrumental in developing effective strategies for target-gene replacement of many different types of mutations, and opens the door for using genome-editing tools to possibly cure a broad range of genetic diseases.
Techniques that modify DNA notably the CRISPR-Cas9 system have generally been most effective in dividing cells; such as those in the skin or the gut, using the cells normal DNA repair mechanisms. The Izpisua Belmonte lab previously showed that their CRISPR/Cas9-based gene-editing technology, called HITI (for homology-independent targeted integration); could target both dividing and non-dividing cells.
Technology for genome editing
Protein-coding regions function like recipes for making proteins; while areas called non-coding regions act as chefs deciding how much food to make. These non-coding regions make up the vast majority of DNA (~98%); and regulate many cellular functions including turning genes off and on; so could be a valuable target for future gene therapies.
This study trying to create a versatile tool to target these non-coding regions of the DNA; which would not affect the function of the gene; and enable the targeting of a broad range of mutations and cell types. As a proof-of-concept, we focused on a mouse model of premature aging caused by a mutation that is difficult to repair using existing genome-editing tools.
The new gene knock-in method, which the scientists call SATI; (short for intercellular linearizing Single homology Arm donor mediated intron-Targeting Integration) is an advancement of the previous HITI method to enable it to target additional areas of the genome. SATI works by inserting a normal copy of the problematic gene; into the non-coding region of the DNA before the mutation site.
This new gene then becomes integrated into the genome; alongside the old gene via one of several DNA repair pathways, relieving the organism of the detrimental effects of the original; mutated gene, without risking damage associated with fully replacing it.