Researchers led by Patrick Hsu, PhD, have discovered an RNA-guided system that enables modular and programmable DNA insertions, excisions, and inversions—another sizeable step for programmable genome engineering

Nature paper: https://doi.org/10.1038/s41586-024-07570-2

Video explainer of technique: https://www.youtube.com/watch?v=hJ7zvZTxgT4

TLDR: New genomic editing technique discovered that scales much better than CRISPR. It can modify entire genetic sequences rather than individual genes.

> In January of this year, researchers in Hsu’s laboratory (he is also assistant professor of bioengineering and Deb Faculty Fellow at the University of California, Berkeley) [posted a preprint on bioRxiv](https://www.biorxiv.org/content/10.1101/2024.01.24.577089v1) in which they claim to have discovered a new class of natural single-effector RNA-guided systems. That story, now peer reviewed, is published online today in Nature.

> These systems retain the key property of programmability from RNAi and CRISPR, while enabling large-scale genome design beyond RNA and DNA cleavage. These modular, bi-specific bridge RNAs can be reprogrammed to enable sequence-specific fundamental DNA rearrangements, potentially accelerating the advancement of genome design.

…

> Then came the eureka moment, where the entire picture of their computational and experimental data came together. Perry and Durrant had discovered a single-effector recombinase system that uses a bridge RNA with two distinct binding loops that can be independently reprogrammed to bind and recombine diverse DNA sequences. “We realized it was programmable on both [the donor and target] ends, which was completely unprecedented,” said Perry.

> The team went on to demonstrate that the modularity of each loop of the bridge RNA can facilitate the recombinase system to execute sequence-specific insertions, inversions, and excisions. This meant that the bridge RNA-guided single effector system provided “a unified, programmable, and modular mechanism for the fundamental DNA rearrangements required for genome design,” says Hsu. “We discovered a conceptually distinct mechanism of RNA-guided self recognition for a mobile genetic element and capitalized upon this mechanistic feature to enable a [new method of genetic engineering](https://www.youtube.com/watch?v=hJ7zvZTxgT4).”