Introducing a powerful, programmable new mechanism for genome design: DNA recombination with bridge RNAs, discovered by Arc’s Patrick Hsu lab. As the first natural RNA-guided DNA recombinase, this system enables insertion, excision, or inversion of any two DNA sequences. CRISPR has revolutionized gene editing. But for true large-scale genome design, scientists need a precise and programmable way to rearrange large segments of DNA. The bridge recombinase programmably joins two DNA molecules without exposing DNA breaks, overcoming key limitations of existing approaches. How does it work? The recombinase enzyme relies on a noncoding bridge RNA with two loops. One loop binds the donor DNA and the other loop binds the target DNA – the first example of a bispecific guide RNA. The two loops can be independently programmed to control the directionality of the DNA rearrangement. The new discovery is the result of two and a half years of collaboration with scientists across disciplines, institutes, and continents. The research was led by Patrick Hsu Matthew Durrant Nicholas Perry, with significant contributions from Arc Core Investigator Silvana Konermann’s lab, and the Nishimasu lab at the The University of Tokyo, led by Hiroshi Nishimasu. It is an early example of scientific output from Arc Institute’s collaborative model, which blends expert scientific staff with graduate students from Arc’s partner universities–UC Berkeley, Stanford University, and UCSF–in an interdisciplinary research environment across computational and experimental science. “We are excited to explore new applications that stem from our team’s interdisciplinary research across computation, genetics, biochemistry, bioengineering, and structural biology—the deep synergistic work that Arc was specifically designed to accelerate," said Hsu. Read more: https://lnkd.in/gipcKrFn First study in @Nature: https://lnkd.in/g6RwBQGE Second study in @Nature: https://lnkd.in/gHSh9tSb Learn about job opportunities at Arc: https://lnkd.in/gyfgqR3n Video by Visual Science
This is huge, especially in tandem with various delivery systems that can be tailored to cell subsets.
I covered this in the last issue of my newsletter! Follow the link in bio to read it!