Gene editing advancements in recent years have unlocked new potentials in how humans think about genetic possibilities. However, a new study from an international team of researchers detailed a new gene editing technique that could modify a single DNA base with "absolute precision" in the human genome.
To date, the process developed by the Japanese team could radically reshape what could be possible with gene editing. The team called the technology MhAX which stands for Microhomology-Assisted eXcision. The method guides the cell to repair itself by design and provides pairs of genetically matched cells for studying disease-related cell mutations, the team noted in a press release.
The team concentrated their research on single mutations in DNA, AKA single nucleotide polymorphisms or SNPs. SNPs are the most common style of variation within the human genome. Over 10 million SNPs exist, and some of the most famous include heart disease, diabetes, and Alzheimers.
The researchers wanted to take a closer look at connecting SNPs with largely hereditary diseases. However, in order to do that, the team needed to compare a 'twin' cell that was genetically matched in every single way. The trick was getting twin cells to differ by only one SNP. Thus the need for a process like MhAX to streamline a way to create twin cells.
The team placed an SNP modification alonside a fluorescent reporter gene that helps the researchers look for and find modified cells. They then engineered a duplicate DNA sequence on each side of the fluorescent gene. These would become sites for the CRISPR editing to later cut the DNA. The team then used a repair system called microhomolog-mediated end joining (MMEJ) to take out the fluorescent gene.
And the entire process left the researchers with a single-base edit SNP at the end of the project.
The process was long and not nearly as 'simple' as it is described, according to the team's authors on the study.
"Usually we need to add a gene for antibiotic resistance along with the SNP to overcome low efficiency," said Shin-Il Kim, an assistant professor in the Woltjen lab and co-first author of the study. "Since that adds another change to the genome, we also need a way to remove it."
Associate professor Knut Woltjen served as the lead on the project. He said his inspiration for the MhAX technology came from watching DNA naturally respond to external forces and repair itself.
"To make MhAX work, we duplicate DNA sequences which are already present in the genome. We then let the cells resolve this duplication. At the same time, the cells decide which SNPs will remain after repair," he says. "One experiment results in the full spectrum of possible SNP genotypes."
The team with Woltjen's lab has already used creating and correcting other SNPs. They're currently working toward figuring out the genetic cause of severe diabetes in younger patients.
"Our goal is to generate gene editing technologies which improve our understanding of disease mechanisms, and ultimately lead to therapies," said Woltjen, "We're confident that MhAX will have broad applicability in current human disease research, and beyond."