The Bridge Recombination Mechanism — Next Generation Genome Design

Researchers have discovered the bridge recombinase mechanism, a precise and powerful tool to recombine and rearrange DNA in a programmable way. Going far beyond programmable genetic scissors like CRISPR, the bridge recombinase mechanism enables scientists to specify not only the target DNA to be modified, but also the donor material to be recognized, so they can insert new, functional genetic material, cut out faulty DNA, or invert any two sequences of interest. "The bridge RNA system is a fundamentally new mechanism for biological programming," said Hsu, senior author of the study  .

Transcript

00:00:00 What if we had the capability to recombine, insert, excise, or invert any two pieces of DNA A team led by scientists at the Arc Institute has discovered that jumping genes from the IS110 family produce a new kind of non-coding RNA guide that enables fully programmable DNA rearrangements Uniquely, this Bridge RNA contains two loops:

00:00:27 one, that guides the recombinase enzyme to the genomic target site, and a second that recognizes the donor DNA Once bound to both DNA substrates, the recombinase forms composite active sites to swap the top strands between the two DNA molecules. Following strand exchange, The DNA forms a holiday junction-like intermediate. Finally, the bottom strands are exchanged to fully recombine the two DNA molecules,

00:00:55 without creating unwanted DNA breaks. Bridge RNA loops can be independently reprogrammed to insert, excise or invert any two DNA sites of interest, allowing us to make flexible genome manipulations beyond what's possible with CRISPR. Now for the first time, the Bridge Recombination system gives us precise control over large scale DNA rearrangements enabling a new generation of genome editing and design.