Secret People: Jennifer Doudna

Jennifer Anne Doudna ForMemRS is an American biochemist who has done pioneering work in CRISPR gene editing, and made other fundamental contributions in biochemistry and genetics. She received the 2020 Nobel Prize in Chemistry, with Emmanuelle Charpentier, “for the development of a method for genome editing.

CRISPR-Cas9 genome editing discovery

Doudna was introduced to CRISPR by Jillian Banfield in 2006 who had found Doudna by way of a Google search, having typed “RNAi and UC Berkeley” into her browser, and Doudna’s name came up at the top of the list. In 2012, Doudna and her colleagues made a new discovery that reduces the time and work needed to edit genomic DNA. Their discovery relies on a protein named Cas9 found in the Streptococcus bacterial “CRISPR” immune system that cooperates with guide RNA and works like scissors. The protein attacks its prey, the DNA of viruses, and slices it up, preventing it from infecting the bacterium.[11] This system was first discovered by Yoshizumi Ishino and colleagues in 1987[35] and later characterized by Francisco Mojica, but Doudna and Emmanuelle Charpentier showed for the first time that they could use different RNAs to program it to cut and edit different DNAs.[11]

As CRISPR becomes increasingly used to edit multicellular organisms, Doudna continues to be called upon to serve as a thought-leader on the ethics of changing an organism’s function using CRISPR technology.[37] Their discovery has since been further developed by many research groups[14] for applications ranging from fundamental cell biology, plant, and animal research to treatments for diseases including sickle cell anemiacystic fibrosisHuntington’s disease, and HIV.[10][20] Doudna and several other leading biologists called for a worldwide moratorium on any clinical application of gene editing using CRISPR.[38][39] Doudna supports the usage of CRISPR in somatic gene editing, gene alterations which do not get passed to the next generation, but not germline gene editing.[40]CRISPR-Cas9 complex

The CRISPR system created a new straightforward way to edit DNA and there was a rush to patent the technique.[10] Doudna and UC Berkeley collaborators applied for a patent and so did a group at the Broad Institute affiliated with the Massachusetts Institute of Technology and Harvard.[41] Feng Zhang at the Broad Institute had shown that CRISPR-Cas9 could edit genes in cultured human cells a few months after Doudna and Charpentier published their method.[20] Before the UC Berkeley patent application was decided, a patent was granted to the Broad investigators and UC Berkeley filed a lawsuit against the decision.[41] In 2017, the court decided in favor of the Broad Institute, who claimed that they had initiated the research earliest and had first applied it to human cell engineering thus supporting editing in human cells with evidence but that the UC Berkeley group had only suggested this application.[41] UC Berkeley appealed on grounds that they had clearly discussed and spelled out how to do the application the Broad had pursued.[42] In September 2018, the appeals court decided in favor of the Broad Institute’s patent.[43] Meanwhile, UC Berkeley and co-applicants’ patent to cover the general technique was also granted.[44] To further cloud the issue, in Europe the claim of the Broad Institute, to have initiated the research first, was disallowed.[45] The rejection was due to a procedural flaw in the application involving a different set of personnel listed in the lawsuit and the patent application, leading to speculation that the UC Berkeley group would prevail in Europe.[45] Doudna cofounded Caribou Biosciences, a company to commercialize CRISPR technology, in 2011.[46] In September 2013, Doudna cofounded Editas Medicine with Zhang and others despite their legal battles, but she quit in June 2014; Charpentier then invited her to join CRISPR Therapeutics, but she declined following the “divorce”-like experience at Editas.[47] Doudna is also a cofounder of Caribou spin-off Intellia Therapeutics[48][49] and Scribe Therapeutics, which pioneered CasX, a more compact, next-generation Cas9 which can efficiently cut DNA.[50]

In addition to the CRISPR breakthrough, Doudna has discovered that the hepatitis C virus utilizes an unusual strategy to synthesize viral proteins.[51] This work could lead to new drugs to stop infections without causing harm to the tissues of the body.[51]

Article thanks to CityXcape and Wikipedia

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