Researchers in Spain have revived an ancient CRISPR protein that is millions and even billions of years old. Not only are they still capable of editing human cells, they are also more versatile than the latest versions, paving the way for new and improved synthetic CRISPR gene-editing tools.
The CRISPR system evolved in bacteria as a self-defense mechanism. When a bacterium is infected with a virus, it uses the CRISPR enzyme to cut out and store pieces of the pathogen’s DNA. If the bacteria later encounter a virus of the same type, they can recognize it based on the DNA fragment and fight it off more effectively.
About ten years ago, scientists discovered that this mechanism of recognizing and cutting DNA could be exploited and used to develop powerful gene-editing tools. The resulting CRISPR-Cas9 system acts like molecular scissors, snipping pieces of DNA from cells and replacing them with new ones. This shows promise as a powerful tool for treating disease, improving crops, and manipulating bacteria for intriguing new purposes.
For a new study, researchers at CIC nanoGUNE in Spain set out to chart the evolution of CRISPR in microorganisms. To do so, they used a technique called ancestral sequence reconstruction. This technique used specially designed algorithms to analyze and compare the genomes of organisms to determine what the genomes of their common ancestors looked like.
This led the team to identify and synthesize Cas enzymes that were likely used by ancient microbes dating from 37 to 2.6 billion years ago. Testing in human cells confirmed that these ancestral enzymes are still functional in performing gene editing.
Perhaps unsurprisingly, ancient enzymes were much simpler than modern enzymes, with evolutionary imprints at work. Interestingly, however, that may make it more versatile than its niche-focused offspring.
“The current system is very complex and adapted to work in bacteria,” said lead investigator of the study, Raul Pérez-Jiménez. “There are also certain molecular limitations that limit its use when the system is used outside this environment, e.g., in human cells, which are rejected by the immune system. parts, giving these systems greater versatility for new applications.”
The team could use this breakthrough to generate new enzymes that target regions of the genome that current enzymes cannot edit, potentially opening new avenues for the treatment of disease and other gene-editing advances. said to be sexual.
A study was published in a journal natural microbiology.
Source: CIC nanoGUNE
