Gene Editing: The Latest Version Of CRISPR Can Switch Single Letters Of DNA

A new improvement to the CRISPR gene editing system that’s taken the world by storm can switch single letters of the genome safely and efficiently

CRISPR has fantastic potential, but there are remaining concerns over accuracy and off-target cuts. It essentially makes a snip in a target sequence of DNA which allows you to slip in a new section in place of the old, but it’s not entirely clear yet whether it snips in other places too. This has produced safety concerns when it comes to humans. While serious editing will need more than single letter switches, a huge range of genetic diseases like Tay-Sachs and cystic fibrosis, are caused by a single letter substitution in a sequence of DNA that messes up the gene’s function or translation. This makes them ideal targets for a newly modified version of CRISPR. 

A switch up

There have already been a few tweaked versions of the original technology that allow you to do different things, like turning specific genes off instead of editing them. The latest addition unveiled in Nature is one of the smartest yet, and allows single letter substitutions which could conceivably correct the point mutations that causes these diseases. 

“Most known human genetic variations associated with disease are point mutations. Current gene-editing methods aren’t particularly good at correcting those”

The new technology switches single nucleotides, shown above in colour

This new invention is great because it doesn’t actually cut the target DNA, which makes it far safer. The research team used a ‘dead’ version of the enzyme called Cas9 that makes a double stranded cut in DNA. Cas9 is guided by a CRISPR RNA sequence. The dead version of Cas9 still binds to DNA but doesn’t make a cut, so the team added extra proteins to it that can switch nucleotides – turning a C to a T and a G to an A. 

There are a total of 12 possible letter combination changes however, so the system isn’t perfect yet but it’s a big step up. There are over 3000 diseases that could be corrected by the two switches above however not to mention fixing possible cancerous mutations, and attaching novel proteins could enable creation of multiple versions that can perform different letter substitutions. 

If you’re not the clued up about CRISPR then check out this video by the McGovern Institute for Brain Research:

Read more at STAT News