Posted on 4 December 2015
After recent good news regarding the accuracy of famed CRISPR-Cas9, a new form has been engineered that’s even more accurate than the original.
A string of positive developments
If you’ve been reading the news lately, you may know recent analysis of the gene editing system CRISPR-Cas9 has had a string of positive updates. We found out it’s surprisingly more accurate than we first believed, which bodes well as scientists across the world start thinking about the move into human models.
Even with this news, we can do better
Considering the incredible potential of gene editing, whether for ‘good or ill’ it’s too late to ignore the phenomenon. So if it’s now an inevitable technology, which many longevity proponents are optimistic about, then the aim is to introduce it safely and reliably. The team that co-discovered the system has now produced an updated, tweaked version that offers increased accuracy (and therefore safety).
Reducing off-target binding even more
The CRISPR-Cas9 editing approach consists of a guiding sequence of RNA that hones into a specific DNA sequence, and the Cas9 enzyme which binds and snips. Although Cas9 is great at cutting its target site, there are fears of off-target cuts happening too, especially if we move onto human patients. In an effort to improve safety, the MIT team scanned the structure of Cas9 with the aim of designing a ‘better’ version.
Changing the charge
The researchers knew the DNA binding to the enzyme was negatively charged, and the active site of Cas9 must be predominantly positively charged to lock onto its target. Cas9 is made up of over 1500 amino acids, and by changing 3 of these at the key binding groove, they hoped to increase reliability.
When they tested the newly made enzyme, they found the extra positive charges made off-target binding virtually undetectable. This is great news for the gene editing field; if we could demonstrate a robust safety record, then gene editing will be able to move much quicker. While the system is not yet ‘perfect’, and further improvements are needed, it’s a welcome step forward.
“Many of the safety concerns are related to off-target effects.We hope the development of eSpCas9 will help address some of those concerns, but we certainly don’t see this as a magic bullet. The field is advancing at a rapid pace, and there is still a lot to learn before we can consider applying this technology for clinical use.”
Read more at MIT News
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