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Biology 31 Jan 2017

Pioneers of the genetic “copy-paste” earn Frontiers of Knowledge award

The BBVA Foundation has bestowed its Frontiers of Knowledge Award in the Biomedicine category on Emmanuelle Charpentier, Jennifer Doudna and Francisco Martínez Mojica, for igniting “the revolution in biology permitted by CRISPR/Cas 9 techniques.” These tools facilitate genome modification with an unprecedented degree of precision and far more cheaply and straightforwardly than any previous method.  Not unlike today’s word processing programs, CRISPR/Cas 9 is able to “cut & paste” several genes at the same time.

The prize jury, formed by eight European and American experts, were keen to highlight the vision and perseverance of Martínez Mojica in exploring a biological problem which at the time interested no one, but would enable the flowering of a new revolutionary technique.

“Martínez Mojica identified CRISPR sequences in microorganisms and postulated their role as an adaptive defense system against viruses;  Charpentier and Doudna elucidated the molecular mechanism of CRISPR/Cas 9 action and demonstrated its potential use as a universal tool for genome editing, paving the way for a multitude of applications in essentially any organism,” reads the award’s citation.

Since it came into play as a genome editing tool in 2012, CRISPR/Cas 9 has been used to search for new treatments against numerous diseases – including cancer and AIDS – as well as to breed new plant varieties and in environmental applications.

Clinical trials in human subjects already underway

The technique has cut the time required to voluntarily alter the genome from years to a matter of weeks, and many have hailed it as the democratization of genetic editing, because it puts the technique within reach of any molecular biology lab.

Laboratories in China and the United States plan to shortly use it in clinical trials in humans as a treatment against diverse types of cancer.  If these trials support the safety of gene editing in humans, we may soon see CRISPR/Cas 9-based treatments being tested for use against multiple ailments.

The revolutionary gene editing technique has Spain as its birthplace.  Francisco Juan Martínez Mojica (Elche, 1963), a microbiologist at the University of Alicante, gave CRISPR its name, and his was the vital basic discovery, in 2003, that set its development in motion.

Studying the genome of different microorganisms in the Salinas de Santa Pola, he discovered that regularly spaced repeat sequences occurred abundantly throughout the microbial world, pointing to “an ancestral origin and major biological relevance.”

The repeat sequences, it turns out, form part of the immune system of microorganisms, a defense mechanism that remembers and repels aggressors, and can pass the memory on to the next generation.

Their CRISPR, as such, acts as a kind of genetic vaccine:  the spaces between the repeat sequences carry fragments of the aggressor species’ DNA; molecular signatures that can be recognized if they attack again.

“The discovery that microorganisms, like us, are equipped with a defense system was entirely astounding and unexpected,” says Mojica.  This finding sparked a growing interest in CRISPR, with groups the world over competing to describe its exact mode of functioning.

Replicating the “cut & paste” system in the laboratory

Emmanuelle Charpentier (Max Planck Institute for Infection Biology) and Jennifer Doudna  (University of California, Berkeley) proposed the development of a precision genome editing technique based on this finding.

By 2012, Charpentier and Doudna had managed to artificially reproduce the CRISPR/Cas 9 system, which in nature, destroys attacking microorganisms by slicing their DNA. Specifically, the CRISPR structure – the repeat sequences and virus fragments – serve as a guide which steers the “scissors” – the Cas 9– enzyme – to the specific DNA region targeted for cleaving.

“If you don’t understand a bacterial mechanism, you will never get the idea that leads to a gene-editing technique.”

Charpentier and Doudna reproduced this mechanism in the laboratory, and were able to demonstrate its use as “a powerful genome-editing tool that can be programmed to recognize any fragment of DNA,” Charpentier explains.

Doudna shares her enthusiasm about the technique’s promise in biomedicine “both for its potential to advanced fundamental research about cells and how they function, but also as a tool for curing genetic disease.”

The Berkeley researcher predicts that some of its first applications “will target the DNA mutation that causes sickle-cell anemia, and also diseases that affect the eyes.”

For his part, Martínez Mojica Even declares himself “thrilled” at receiving the Frontiers of Knowledge Award. And uses the occasion to champion the cause of basic science:  “There can be no advances without funding for basic research; if you don’t know how an organism functions, you can’t fight disease; if you don’t understand a bacterial mechanism, you will never get the idea that leads to a gene-editing technique… Each basic science project is a tree that yields not one but many fruits.”

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