Next-Generation Genome Editing: Scientists Discover Powerful New RNA-Guided System

A team of researchers at the Arc Institute have developed an RNA-guided system that engineers precise, programmable DNA recombination. It is a much-needed, more versatile alternative to CRISPR for editing genomes with much greater precision.

Arc researchers found a new mechanism of precise DNA recombination. A novel system, called the “bridge recombinase,” represents an advanced technology in programmable DNA rearrangement and sets modern standards in genome design. This finding has been published in Nature under the title “Bridge RNAs direct programmable recombination of target and donor DNA”, presenting a new tool to edit genetic material flawlessly and easier than with the help of CRISPR.

This DNA recombinase is unique in that it uses a noncoding RNA molecule to specify the target and donor DNA sequences with unprecedented precision. The researchers believe that this could become one of the game-changing tools in editing and manipulating genomes for everything from gene therapy to synthetic biology.

How Does the Bridge Recombination System Work?

The Bridge recombination system provides a fine tool that allows manipulation of genetic material in such a way as to introduce complex changes within DNA: insertion, deletion, and even rearrangement of programmable segments. This surpasses most of the conventional technologies like CRISPR in allowing full genomic changes, including sequence-specific insertions, excisions, and inversions.

Wrapped around this breakthrough is the “bridge RNA,” a bi-specific guide orchestrating recombination by binding with target and donor DNA. While native versions of such “jumping genes,” emanating from transposable elements such as insertion sequence 110 (IS110), naturally conduct DNA manipulation, it is the precision driven by RNA guidance that constitutes the key innovation here. Each of the bridge RNA loops can be independently programmed to allow the insertion of nearly any DNA sequence into a location of choice in the genome. Lead author Nick Perry describes it as a “universal adapter” that allows accurate and flexible genome editing.

What Lies Ahead for Genome Editing.

This system now represents an advance in genome editing and offers a level of precision and flexibility simply unavailable in current technologies. The tool may very well unleash a whole range of new possibilities for medical research and biotechnology by programmatically changing DNA at higher orders. This, to someone deeply invested in the future of genetic engineering, can mean driving breakthroughs in everything from gene therapies to synthetic biology and push the boundaries of what we can achieve in science.

Dig deeper into the details here.