Emmanuelle Charpentier (left) and Jennifer Doudna (right) won this year’s chemistry Nobel for the development of a powerful way to change DNA.

The Nobel Prize in Chemistry has been awarded to two scientists who transformed an obscure bacterial immune mechanism, commonly called CRISPR, into a tool that can simply and cheaply edit the genomes of everything from wheat to mosquitoes to humans.

The award went jointly to Emmanuelle Charpentier of Max Planck Unit for the Science of Pathogens and Jennifer Doudna of the University of California, Berkeley, “for the development of a method for genome editing.They first showed that CRISPR—which stands for clustered regularly interspaced short palindromic repeats—could edit DNA in an in vitro system in a paper published in the 28 June 2012 issue of Science. Their discovery was rapidly expanded on by many others and soon made CRISPR a common tool in labs around the world. The genome editor spawned industries working on making new medicines, agricultural products, and ways to control pests.

Many scientists anticipated that Feng Zhang of the Broad Institute, who showed 6 months later that CRISPR worked in mammalian cells, would share the prize. The institutions of the three scientists are locked in a fierce patent battle over who deserves the intellectual property rights to CRISPR’s discovery, which some estimate could be worth billions of dollars.

The ability to cut DNA where you want has revolutionized the life sciences. The genetic scissors were discovered 8 years ago, but have already benefited humankind greatly,” Pernilla Wittung Stafshede, a chemical biologist at the Chalmers University of Technology, said at the prize briefing.

CRISPR was also used in one of the most controversial biomedical experiments of the past decade, when a Chinese scientist edited the genomes of human embryos, resulting in the birth of three babies with altered genes. He was widely condemned and eventually sentenced to jail in China, a country that has become a leader in other areas of CRISPR research.

Although scientists were not surprised Doudna and Charpentier won the prize, Charpentier was stunned. “As much as I have been awarded a number of prizes, it’s something you hear, but you don’t completely connect,” she said in a phone call with the Nobel Prize officials. “I was told a number of times that when it happens, you’re very surprised and feel that it’s not real.”

Bacteria use the original form of CRISPR to fend off viruses, slicing up their DNA. “I am so pleased that the [Nobel] award description led off with the bacterial adaptive immune response, which is a truly amazing system, thus highlighting how basic research is absolutely critical for medical applications,” says CRISPR researcher Maria Jasin of the Sloan Kettering Institute.

Doudna and Charpentier—who is originally from France and at the time of the discovery worked at Umeå University—showed they could program a small strip of what they called “guide RNA” to carry a bacterial CRISPR-associated (Cas) enzyme to exact DNA sequences, allowing them to target specific genes. Cas then cuts the double-stranded DNA. In many cases, the DNA repair mechanism of the cell makes errors, which can cripple a gene—knocking out a gene in this fashion is an effective way of studying its normal role. CRISPR also allows researchers to insert a new stretch of DNA at the cut site.

Harvard University chemist George Church says the Nobel committee made “a really great choice.” Church published a study showing CRISPR could edit mammalian cells at the same time as Zhang, who previously was a postdoc in his lab. But Church doesn’t think either of them was slighted by not being included in the prize. As he sees it, Charpentier and Doudna made a discovery, which is what the committee prefers to reward, and he and Zhang were inventors. “If anyone wants any tips on how not win a Nobel Prize, it’s pretty easy,” Church says. “I’ve carefully avoided all this kind of brouhaha by focusing on inventions.” And, he says, Zhang is young. “Feng Zhang is so full of creative ideas that I have no doubt that he will get one or two in the future.”

Tom Welton, president of the Royal Society of Chemistry, said he was “hugely pleased to see that the Nobel committee has chosen to honor two leading women in active research.” This year’s prize is the first time any science Nobel has gone to an all-female team.

Many genome editors existed before CRISPR, but using them was time consuming, cumbersome, and expensive. CRISPR not only works with remarkable ease and speed, it also is the first editor that allows researchers to alter several genes in a single experiment. Rudolf Jaenisch of the Massachusetts Institute of Technology, whose group published one of the first studies of CRISPR-edited mice, said “any idiot can do it.” (Watch this story’s reporter fail at CRISPR, however.)

Rodolphe Barrangou, a researcher at North Carolina State University who began using bacteria’s CRISPR mechanism in 2007 to make yogurt cultures that were resistant to infection, says the prize is “a great opportunity to celebrate pioneers in the field.” Doudna and Charpentier, he says, “developed an amazing technology that enabled the scientific community and democratized genome editing.” He says before their work, “relatively few people cared about CRISPR.”

Fyodor Urnov, a CRISPR researcher who works with Doudna, calls it “the most deserved Nobel Prize of the past 20 years.” Doudna’s and Charpentier’s discovery “changed everything for the better,” says Urnov, who previously worked on a more cumbersome gene editor called zinc fingers. “We can improve the world around us in extraordinary ways,” he says, noting that a CRISPR application has already cured a person of sickle cell disease. “The 21st century will be the age of CRISPR—thanks to Jennifer and Emmanuelle.”

Jinek et al., “A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity,” Science 337, 6096 (17 Aug 2012)

Jinek et al., “Structures of Cas9 Endonucleases Reveal RNA-Mediated Conformational Activation,” Science 343, 6176 (14 Mar 2014)

Baltimore et al., “A prudent path forward for genomic engineering and germline gene modification,” Science 348, 6230 (3 Apr 2015)

Taylor et al., “Structures of the CRISPR-Cmr complex reveal mode of RNA target positioning,” Science 348, 6234 (1 May 2015)

Jiang et al., “A Cas9–guide RNA complex preorganized for target DNA recognition,” Science 348, 6242 (26 Jun 2015)

Jiang et al., “Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage,” Science 351, 6275 (19 Feb 2016)

Dagdas, “A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9,” Science Advances 3, 8 (4 Aug 2017)

© 2020 American Association for the Advancement of Science. All rights Reserved. AAAS is a partner of HINARI, NOW, REALLY, CHORUS, CLOCKSS, CrossRef and COUNTER.

Source: https://www.sciencemag.org/news/2020/10/crispr-revolutionary-genetic-scissors-honored-chemistry-nobel

Emmanuelle Charpentier, Nobel Prize in Chemistry, Jennifer Doudna, CRISPR, Chemistry, Genome editing

World news – US – CRISPR, the revolutionary genetic ‘scissors,’ honored by Chemistry Nobel

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