When the most basic research comes to the aid of the most applied: the origin of CRISPR-Cas

  Francis Mojica, a microbiologist at the University of Alicante, and Lluis Montoliu, a CIBERER researcher at the CNB-CSIC, have published a joint review article on the CRISPR-Cas technique in the journal Trends in Microbiology , of the Cell Press group, one of the the most important scientific publications internationally. In science, on many occasions, great revolutions have their origin in the smallest beings. This is the case of CRISPR-Cas, the most revolutionary gene editing technique of the last decades. A secret jealously guarded by bacteria for millions of years until a microbiologist, Francis Mojica, from Alicante, discovered it.

This review article describes the history of this technique from the point of view of a microbiologist and geneticist. "For the first time - indicate the authors -, we have joined two experts in very disparate areas (a basic researcher who works with microorganisms and an expert in mammalian genetics) to give this novel technique the dimension it deserves"

The article highlights the basic science and work of all the microbiologists who have investigated the defense system of bacteria for more than two decades so that, in the last three years, geneticists have been able to take advantage of the system for gene editing.

“The CRISPR-Cas system has evolved in bacteria over millions of years. What we use today for the benefit of mammals derives from millennia of evolutionary optimization in bacteria ”, explains Francis Mojica, who was the discoverer of CRISPR in archaea and father of the name of the technique.

For his part, Lluis Montoliu is a pioneer and reference in Spain in the application of the genetic cutter technique and recalls the great technical difficulties that the modification of the mammalian genome entailed for decades. "The ease and efficiency that the CRISPR-Cas system offers us is really surprising and very exciting," says the scientist. But it is important not to forget the origin of this technique: it was microorganisms and nature that, once again, made an innovative solution available to us ”.

In the review, the two researchers collect the history of CRISPR-Cas over the past 20 years. From the first signs of its existence in the late 80s, through the studies that identified it as an immune defense system of bacteria against viruses and other infectious elements.

In 2012, for the first time, it was proposed that the CRISPR-Cas system could be used as a highly efficient gene editing tool in any organism. “That's when things got rushed: it caught the attention of genetic engineering experts and in the next three years the technique rose to prominence. In 2015, it became the discovery of the year according to Science and was on the front page of newspapers around the world, ”the authors say.

In the last three years, CRISPR-Cas tools have revolutionized biology and biomedicine. The technique makes it possible to generate very specific mutations in the genome of any living being. One of the most relevant applications consists in the generation of animal and cellular models for the study of human diseases. According to Montoliu, who focuses his research on the study of rare diseases such as albinism, "it is now easier to reproduce pathologies such as albinism in animals in order to study their etiology, search for new early diagnosis methods and possible treatments."

The authors admit that there is still work to be done for both microbiologists and geneticists, “perhaps there are still other similar systems in prokaryotes to be discovered that facilitate the genetic modification of eukaryotic organisms. It may have already been described, but we do not yet know its usefulness. Meanwhile, we have to continue working to improve this new tool so that it can be applied in therapy against human genetic diseases ”.