Scientists have developed a novel gene editing tool that could have vast implications for research and therapeutics. This technology is called STITCHR (site-specific target-primed insertion through targeted CRISPR homing of retroelements), and it harnesses retroelements to make anything from a single-base pair edit to changing entire genes or inserting novel coding sequences. The research has indicated that it can also make these highly specific and significant genetic changes without causing unwanted edits. The work has been reported in Nature.
The CRISPR gene editing technology has also been revolutionary, but the CRISPR reagents have to be designed in specific ways, which can limit how and where it is applied to the genome. CRISPR also usually only targets a single sequence, while many genetic diseases happen because of multiple mutations.
"CRISPR has revolutionized how we think about gene editing, but it has limitations. CRISPR can't target every location in the genome, and it can't fix the thousands of mutations present in diseases like cystic fibrosis," explained co-senior study author Omar Abudayyeh, Ph.D.,of Mass General Brigham and Brigham and Women's Hospital (BWH).
STITCHR relies on enzymes that are related to genetic elements known as retrotransposons, or jumping genes.
Some types of retrotransposons known as endogenoous retroviruses are thought to be remnants of ancient viruses, which once moved around the genomes of cells of many different organisms, boosting evolutionary processes. Most of these retrotransposons are thought to be rendered inert in modern humans.
But in this study, the researchers identified a copy-and-paste process that retrotransposons use to move around the genome. Then they searched genomes for one that could be repurposed for use in the lab.
When the best candidate was found, which came from the zebra finch genome, it was combined with an enzyme that cuts one strand of DNA at a time, called a nickase to ease the editing process, and create the STITCHR system.
More work will be needed to refine and test this technology so it can be used in the clinic, but for now, it may have a big impact in labs.
"By studying basic biology in our cells, we can find inspiration for new tools. These can expand our cell engineering capabilities and lead to the creation of new medicines and therapies for both rare and common diseases," said co-corresponding study author Jonathan Gootenberg, Ph.D., of Harvard Medical School, among other appointments.
Sources: Mass General Brigham, Nature
