The breakthrough discovery of a powerful new gene editing tool called bridge RNAs has the potential to significantly advance gene therapy and usher in a new frontier in genome design, researchers say.

Discovered by a team of scientists at the Arc Institute and led by Patrick Hsu, PhD, a University of California, Berkeley, assistant professor of bioengineering, bridge RNAs provide precise control over large-scale DNA rearrangements and make the editing process possible in a single step.

CRISPR, a groundbreaking technology used to edit genes, was already used for COVID rapid tests. And that’s just the beginning. Could it one day eradicate rare diseases or grow organs for transplant? While the technology could potentially lead to new therapeutic approaches to treat heart disease and cancer one day, its biggest application may be for genetic disorders. If it can be copied accurately in human cells, the RNA programmability of this new biological mechanism could eventually allow complex gene editing that could cure genetic diseases that carry hundreds or thousands of genetic mutations,

“Not only can you treat every patient with one therapy for one genetic disease, we can easily reprogram that insertion with a different gene to go to another site, for another genetic disease, and cure everybody for that genetic disease,” said Connor Tou, a biological engineering PhD student at the Massachusetts Institute of Technology who co-authored a piece in Nature discussing the Arc Institute discovery. If this technology works as well as researchers hope it will, “it’s almost like a kind of holy grail.”

Gene or genome editing is when a DNA sequence in a living cell is changed. Three decades ago, the first generation of “programmable biology” was discovered with RNA interference (RNAi). Short RNA sequences could be used to target and shut down specific genes. The second generation came along about a dozen years ago, with the discovery of CRISPR, which stands for clustered regularly interspaced short palindromic repeats. It is an immune system used by microbes to help protect themselves and a powerful molecule and tool that allows genes to be “edited” directly. This was a game changer. What would have taken years and years of research and development could now be done in a matter of days.

“The analogy a lot of people like to use is, instead of having to rebuild the computer every single time, you just upload new software,” said Tou. A CRISPR-linked protein could find and target a precise location in DNA to “edit” by acting like scissors and making a cut. The genetic sequence around that location could then be changed by adding a new DNA fragment, for example. Once a cut is made, it is a multistep, imperfect process of cellular DNA repair. CRISPR can be used to make other types of edits too, such as increasing or decreasing the effects of a gene temporarily. Regardless of the type of editing, the process generally remains limited to small-scale changes.