Mwinde Mwolilo

Today in @ScienceMagazine, we report a new DNA editing technology to seamlessly write massive changes into the right place in the human genome. The reason gene editing hasn't transformed human health is that current gene editing technologies like CRISPR are very limited. The problem with CRISPR is that it cuts up your DNA, and then hopes that unreliable cellular DNA repair will make the wanted edit. @geochurch famously called it genome vandalism. More precise versions of CRISPR only edit less than 100 bases - often only a single base. Therefore, it's not suited to make large changes safely. However, most diseases are not the result of mutations in one location. Instead, their causes are spread all across the 3 billion base pairs in the genome. We found bridge RNAs in bacterial “jumping genes” that allow us to make safe and arbitrary changes (insert, cut out, or flip) to every nucleotide within (up to) a 1 million bp sequence in your DNA. In the paper, we show that we can correct the disease-causing DNA repeats that cause Friedreich's ataxia (which is a rare neurological disease). The same approach could be applied to Huntington’s and other repeat expansion disorders. At @arcinstitute, we're working towards a full Turing machine for biology. Evo, our DNA foundation model, helps us design the optimal healthy DNA sequences. And Bridge recombination gives us the ability to seamlessly write these changes into the right place in the genome. This work was a wonderful collaboration with my @arcinstitute cofounder @SKonermann and led by the indefatigable @ntperry13, alongside our amazing bridge editing team: @BartieLiam @dhruvakatrekar @Gabogonzalez515 @mgdurrant @james_jw_pai @AlisonFanton Juliana Martins Masa Hiraizumi @chiaroscurale @hnisimasu

Delighted to share a landmark preprint from our lab, using genome language models and AI agents for biological discovery and genome mining! The stretches of DNA between protein-coding genes are often called the genome’s “dark matter,” but they are far from empty. They encode RNA molecules that sense metabolites, regulate genes, and control some of molecular biology's most important tools (such as programmable genome editors e.g. CRISPR/bridge) Much of this biology is unexplored. One reason is that RNAs can retain similar structures and functions even as their DNA sequences change dramatically, making their relationships difficult to recognize with conventional computational tools