New Gene Editing Tool STITCHR Offers 'One-and-Done' Gene Therapy Approach

Mass General Brigham and Beth Israel Deaconess Medical Center investigators have developed STITCHR, a new gene editing tool. STITCHR can insert therapeutic genes into specific locations without causing unwanted mutations. The system can be formulated completely as RNA, simplifying delivery logistics compared to traditional systems using both RNA and DNA. By inserting an entire gene, the tool offers a "one-and-done" approach. This overcomes hurdles from CRISPR gene editing technology, which is programmed to correct individual mutations. The findings were published in *Nature*. According to co-senior author Omar Abudayyeh, PhD, CRISPR has limitations, including the inability to target every location in the genome and fix thousands of mutations in diseases like cystic fibrosis. Abudayyeh stated their lab aimed to insert large pieces or entire genes to replace faulty ones, targeting every mutation for a disease with a single gene editing construct. STITCHR uses enzymes from retrotransposons, genetic elements found in eukaryotic cells (animals, fungi, and plants). Retrotransposons, often called "jumping genes," move around and insert themselves into the genome. Researchers repurposed their copy-and-paste mechanism to edit genes at specific locations. The research team, including lead study author Christopher Fell, PhD, screened thousands of retrotransposons to identify reprogrammable candidates, which they tested in the lab. They combined a final candidate with the nickase enzyme from the CRISPR gene editing system to seamlessly insert genes, forming the STITCHR system. The researchers plan to enhance the system's efficiency and translate STITCHR for clinical applications. Jonathan Gootenberg, PhD, co-corresponding author, stated that studying basic biology in our cells can inspire new tools, expand cell engineering capabilities, and lead to new medicines and therapies for both rare and common diseases.