Spanish scientists “resurrect” millions of years old proteins to correct human albinism

Spanish scientists have published a study that recreates the enzymes Cas9, molecules that work as scissors that can cut the DNA of any living being at a specific point and that are the basis of the CRISPR system of genetic editing. An enzyme resurrected from extinct organisms that lived billions of years ago.

Since it was conceived in 2012, the technique has revolutionized biomedical research, as it allows to rewrite the “instruction manual” of any organism even if it must be used with caution to avoid introducing potentially dangerous errors in the genome.

CRISPR is the immune system of many bacteria that allows them to incorporate genetic sequences of viruses into their genome: if the virus reappears, CRISPR identifies it and Cas9 kills it. A much older immune system than human.

The Spanish study plans to use a technique that reconstructs the genome of extinct organisms, the so-called “reconstruction of the ancestral sequence”which allowed the recovery of Cas proteins present in extinct microbes the oldest of which date back to 2,600 million years ago.

Proteins extinct from microorganisms that lived 1,000 million, 200 million, 137 million and 37 million years ago were also isolated.

Spanish scientists created new CRISPR systems using these ancient proteins and injected them into human cells. The results, published in Nature Microbiology, show that, despite being so primitive, all proteins are able to modify the genome: the oldest of these proteins can only cut single strands of DNA, but the rest of the newer Cas molecules can already cut human DNA with increasing effectiveness and in fact have been able to correct two genes, TYR and OCA2, that cause albinism.

Biologist Francis Mojica gave his name to CRISPR in his studies of microbes, explains: “this work is important because it opens a huge “toolbox” to create better CRISPR systems”.

Raúl Pérez-Jiménez, researcher at the NanoGUNE Basque Center for Cooperative Research in Nanoscience and co-author of the study, describes in detail the potential of the study: “These are the oldest Cas proteins that have ever been obtained. We think they are like a diamond in the rough. Now we will study how to make them as efficient as the current ones or even better. I’m like a Swiss army knife. They have scissors, corkscrew, needle, screwdriver. They’re probably not the best tools in their class, but they all have them”.

Miguel Ángel Moreno Pelayo, head of genetics at the ospeda
Ramón y Cajal of Madrid and co-author of the work, emphasizes that the reconstruction of ancient proteins opens the possibility of designing new forms of synthetic CRISPR “that do not exist in nature”.