Beyond CRISPR: Bridge Editing Ushers in New Era of Genetic Design

In a groundbreaking study published in Nature, scientists at the ARC Institute have unveiled a new genome engineering technology called “bridge editing.”

This innovative approach could dramatically expand our ability to manipulate DNA, offering unprecedented control over genetic rearrangements.

At the heart of this discovery are jumping genes from the IS110 family, which produce a unique type of non-coding RNA guide. This “bridge RNA” is the key to enabling fully programmable DNA rearrangements.

What sets it apart is its dual-loop structure: one loop guides a recombinase enzyme to the target site in the genome, while the other recognizes the donor DNA.

Here’s how the process works:

1. The bridge RNA binds to both the target and donor DNA.
2. The recombinase enzyme forms composite active sites to exchange the top strands between the two DNA molecules.
3. This creates a holiday junction-like intermediate structure.
4. Finally, the bottom strands are exchanged, completing the recombination without causing unwanted DNA breaks.

The significance of this system lies in its flexibility. Researchers can reprogram the bridge RNA loops independently, allowing them to insert, excise, or invert any two DNA sites of interest.

This capability goes beyond what’s currently possible with CRISPR technology, offering precise control over large-scale DNA rearrangements.

Dr. Patrick Hsu, the study’s senior author and an Arc Institute Core Investigator, emphasized the transformative potential of this discovery: “The bridge RNA system is a fundamentally new mechanism for genome design.” As an Assistant Professor of Bioengineering at the University of California, Berkeley, Dr. Hsu’s work is at the forefront of genetic engineering advancements.

This new technology opens doors to a new generation of genome editing and design. It could potentially revolutionize fields such as genetic research, biotechnology, and medicine by allowing more complex and precise genetic modifications than ever before.

As with any significant scientific breakthrough, the bridge RNA system will likely undergo further research and development. However, its potential to enhance our understanding and manipulation of genetic material marks a significant step forward in the field of genome engineering.